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EVIDENCE SEARCH REPORT
RESEARCH QUESTION: How effective are COVID-19 vaccines? UNIQUE IDENTIFIER: INF122302-01 ESR
CONTEXT: Benefits following dose/second dose; how well it prevents infections; evidence of limiting viral replication or spread; preventing hospitalization; preventing ventilation; preventing “long COVID” (long term symptoms), duration of immunity (natural and vaccinated). Does not include vaccine willingness/acceptance (to be run as a separate search). RESOURCES USED: OVID Medline ClinicalTrials.gov OVID Embase Cochrane Collaboration Clinical Trials Registry PubMed & LitCovid WHO website (COVID-19 Vaccines)
LIMITS/EXCLUSIONS/INCLUSIONS: REFERENCE INTERVIEW COMPLETED: December 23, 2020 DATE: December 28, 2020 LIBRARIAN: Lukas Miller REQUESTOR: Cheryl Walder & Jenny Basran
TEAM: INFECTIOUS DISEASES
SEARCH ALERTS CREATED: Y/N (MEDLINE, ETC.) N SUBJECTS: IMMUNITY; CLINICAL PRESENTATION; INFECTION PREVENTION & CONTROL; CITE AS: Miller, L. How effective are COVID-19 vaccines? 2020 Dec 28; Document no.: INF122302-01 ESR. In: COVID-19 Rapid Evidence Reviews [Internet]. SK: SK COVID Evidence Support Team, c2020. 26 p. (CEST evidence search report)
LIBRARIAN NOTES/COMMENTS
Hello,
The research team acknowledged that more time is needed for global mass vaccinations to roll-out in order for there to be more quality, independent data and evidence to inform these questions. It was decided to conduct an inventory/scan of vaccine trials to support future work spurned by the rollout of vaccines.
Both the Cochrane Collaboration and WHO are tracking vaccine trials and provide summary tables that includes links/URLs to relevant publications or registry entries. I have included a pared-down version of this table below.
I conducted a MEDLINE search to find any publications that might comment on or inform vaccine research for COVID-19. A total of 64 citations are included below (some of which include the published trials/commentary as indicated in the COVID-NMA table).
Thank you, DISCLAIMER This information is provided as a service by the Saskatchewan Health Authority and University of Saskatchewan Libraries. Professional librarians conduct searches of the literature. Results are subject to the limitations of the databases and the specificity, broadness and appropriateness of the search parameters presented by the requester. The Libraries do not represent in any matter that retrie ved citations are complete, accurate or otherwise to be relied upon. The search re sults are only valid as of the date and time at which the search is conducted. The Libraries do not accept responsibility for any loss or damage arising from the use of, or reliance on, search results.
Lukas
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SEARCH RESULTS To obtain full-text articles email [email protected].
SUMMARIES, GUIDELINES & OTHER RESOURCES
COVID-NMA Initiative Vaccines: Living Mapping https://covid-nma.com/vaccines/mapping/ o Table provides a complete list of trials, drawn from the Cochrane Clinical Trial Registry and the WHO clinical trials platform.
Vaccines for COVID-19 Patients (Living Evidence Synthesis) https://covid-nma.com/vaccines/ o The “Description of Primary Studies” table provides general characteristics of identified relevant RCTs, including bias assessments. o The “Trial” column includes links to trial registries and/or published journal articles for the indicated vaccine or manufacturer.
World Health Organization (WHO) Draft landscape of COVID-19 candidate vaccines https://www.who.int/publications/m/item/draft- landscape-of-covid-19-candidate-vaccines o Access to downloadable spreadsheet (.xlsx) – updated twice per week. Compiles detailed information on vaccine candidates including links to trial registries and/or publications (if present).
COVID-19 TRIALS Primary Studies Table (23/12/2020 update)
Trial Type Comparisons Desig Participants Sample Full n size description Intervention 1 Intervention 2 NCT04412538 Inactivate KMS-1 100 EU Adjuvant RCT Healthy N=750 Full Institute of Medical d virus D0/14 Phase SARS-CoV-2 descriptio
Biology (IMB), KMS-1 150 EU Adjuvant 2 serology/DNA n Chinese Academy D0/14 negative of Medical Sciences KMS-1 100 EU Adjuvant adults in tw o (CAMS). D0/28 centres in Che Y,Clin Infect KMS-1 150 EU Adjuvant China Dis,2020 D0/28 Full text Commentary NCT04470427 RNA mRNA-1273 Placebo RCT Healthy N=3035 Full ModernaTX based Phase adults w ith no 1 descriptio
COVE, 2020 vaccine 3 know n history n of SARS- new CoV-2 infection in 99 centers in the US Full text Full text Commentary NCT04324606; Non ChAdOx1 MenACWY RCT Healthy N=1077 Full ISRCTN15281137; replicating Phase adults w ith no descriptio
EudraCT 2020- viral 1/2 history of n 001072-15 vector laboratory University of confirmed Oxford/AstraZenec SARS-CoV-2
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a infection or of Folegatti PM COVID-19- (COV001), Lancet, like 2020 symptoms in five centres in Full text the UK Commentary Commentary NCT04368988 Non 2 dose 25mcg Placebo RCT Healthy adult N=134 Full Novavax replicating NVX-D0/21 Phase volunteers, descriptio
Keech C., N Engl J viral 2 dose 5mcg Placebo 1 SARS-CoV-2 n Med, 2020 vector NVX/M1-D0/21 infection-free Full text 2 dose 25mcg Placebo and no Commentary NVX/M1-D0/21 history of 1 dose 25mcg Placebo SARS-CoV-2 NVX/M1+Placebo infection in -D0/21 tw o centres in Australia. NCT04368728 RNA BNT162b2 Placebo RCT Healthy N=4354 Full BioNTech/Fosun based Phase SARS-CoV-2 8 descriptio
Pharma/Pfizer vaccine 2/3 DNA negative n Polack FP,N Engl J adults in Med,2020 multiple centres in Full text Argentina, Commentary Brazil, Commentary Germany, Commentary South Africa, Commentary Turkey, and Commentary the USA NCT04412538 Inactivate KMS-1 D0/14 Adjuvant RCT Healthy N=192 Full The Institute of d virus KMS-1 D0/28 Adjuvant Phase adults aged descriptio
Medical Biology 1 18 to 59 n (IMB), Chinese years, SARS- Academy of CoV-2 nucleic Medical Sciences acid or (CAM) antibodies Pu J, MedRxiv, negative in a 2020 single centre Full text in China. Commentary ; Commentary NCT04436276 Non Ad26.COV2.S Placebo RCT Healthy N=785 Full Janssen replicating 5x10^10vp Phase SARS-CoV-2 descriptio
Pharmaceutical viral Ad26.COV2.S Placebo 1 nucleic acid n Companies vector 1x10^11vp negative Sadoff adults 18-55 J,MedRxiv,2020 years old and Full text elderly >65 Commentary years old in multiple centres in Belgium and the US NCT04400838 Non ChAdOx1 LD/SD 1/2 doses RCT Healthy N=7548 Full University of replicating MenACWY Phase adults in 18 descriptio
Oxford/AstraZenec viral ChAdOx1 SD/SD 1/2 doses 2/3 centers in the n a vector MenACWY UK Voysey M (COV002), Lancet, 2020 Full text Commentary ISRCTN89951424 Non ChAdOx1 SD/SD MenACWY/salin RCT Healthy N=4088 Full
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University of replicating e Phase SARS-CoV-2 descriptio
Oxford/AstraZenec viral 3 serology/DNA n a vector negative Voysey M adults in six (COV003), Lancet, centres in 2020 Brazil
Full text Commentary NCT04444674 Non ChAdOx1 std 2 Saline RCT Healthy N=2013 Full University of replicating doses Phase adults from descriptio
Oxford/AstraZenec viral 1/2 four studies in n a vector multiple Voysey M centres in (COV005), Lancet, Brazil, South 2020 Africa, and the UK Full text Commentary NCT04368728 RNA BNT162b1 10 Placebo RCT Healthy N=195 Full BioNTech SE, based mcg D1/21 Phase SARS-CoV-2 descriptio
Pfizer vaccine BNT162b1 20 Placebo 1 serology/DNA n Walsh E, N Engl J mcg D1/21 negative Med, 2020 BNT162b1 30 Placebo adults in four Full text mcg D1/21 centres in Commentary BNT162b1 100 Placebo USA mcg D1/21 BNT162b2 10 Placebo mcg D1/21 BNT162b2 20 Placebo mcg D1/21 BNT162b2 30 Placebo mcg D1/21 ChiCTR200003180 Inactivate Inactivated Adjuvant RCT Healthy N=96 Full 9 d virus 2.5mcg-D0/28/56 Phase adults, aged descriptio
Wuhan Institute of Inactivated 5mcg- Adjuvant 1/2 18 to 59 n Biological Products D0/28/56 years, w ithout Co Ltd./Sinopharm Inactivated Adjuvant history Xia S, JAMA, 2020 10mcg-D0/28/56 ofSARS- Full text Inactivated 5mcg- Adjuvant CoV(via on- Commentary D0/14 site inquiry) Inactivated 5mcg- Adjuvant or SARS- D0/21 CoV-2 infection (via serologicalan d nucleic acid test ChiCTR200003245 Inactivate BBIBP-CorV Adjuvant RCT Healthy N=112 Full 9 d virus 8mcg Phase SARS-CoV-2 descriptio
Beijing Institute of BBIBP-CorV Adjuvant 2 serology n Biological 4mcg D0/14 negative Products/Sinophar BBIBP-CorV Adjuvant adults 18-59 m 4mcg D0/21 years old and Xia S, Lancet Infect BBIBP-CorV Adjuvant ?60 years old Dis, 2020 4mcg D0/28 in a single Full text centre in Commentary China NCT04352608 Inactivate CoronaVac 3 Adjuvant RCT Healthy N=600 Full Sinovac d virus mcg D0/14 Phase SARS-CoV-2 descriptio
Zhang Y,Lancet CoronaVac 6 Adjuvant 2 serology/DNA n Infect Dis,2020 mcg D0/14 negative Full text CoronaVac 3 Adjuvant adults in a Commentary mcg D0/28 single centre
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CoronaVac 6 Adjuvant in China mcg D0/28 NCT04341389 Non Adenovirus type- Placebo RCT Healthy adult N=508 Full CanSino Biological replicating 5-vectored Phase volunteers descriptio
Inc./Beijing Institute viral COVID-19 1 × 2 w ith HIV- n of Biotechnology vector 10¹¹ vp negative and Zhu F, The Lancet, SARS-CoV-2 2020 infection-free Full text in a single Commentary centre in Commentary China.
ARTICLES Note: References are sorted by year (newest to oldest)
1. Marian AJ. Current state of vaccine development and targeted therapies for COVID-19: impact of basic science discoveries. Cardiovasc Pathol. 2021;50:107278. DOI: 10.1016/j.carpath.2020.107278 ABSTRACT: Coronavirus disease-19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is closely related to two other coronaviruses that caused disease epidemic breakouts in humans in the last 2 decades, namely, severe acute respiratory distress syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). The similarities have enabled the scientists to apply the basic scientific discoveries garnered from studying the structure and modus operandi of SARS-CoV and MERS-CoV to develop therapies that specifically target SARS- CoV-2 and to develop vaccines to prevent COVID-19. Targeted therapies including the use of antibodies to prevent virus entry, nucleotide analogues to prevent viral replication, and inhibitors of proteases to prevent virion formation, among others, are being tested for their clinical efficacy. Likewise, complete sequencing of the SARS-CoV-2 and identification of its structural and nonstructural proteins have enabled development of RNA-, DNA-, and peptide-based vaccines as well attenuated viral vaccines to instigate the host-immune responses. The clinical impacts of the basic science discoveries are amply evident on the rapid pace of progress in developing specific antiviral therapies and vaccines against SARS-CoV-2. The progress emphasizes the merit of discovering the fundamental scientific elements, regardless of whether or not they have apparent or immediate clinical applications. URL: https://www.ncbi.nlm.nih.gov/pubmed/32889088 DOI: 10.1016/j.carpath.2020.107278
2. Xia S, Zhang Y, Wang Y, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial. The Lancet Infectious Diseases. 2021;21(1):39-51. DOI: 10.1016/s1473-3099(20)30831-8 DOI: 10.1016/s1473-3099(20)30831-8
3. Al-Kassmy J, Pedersen J, Kobinger G. Vaccine Candidates against Coronavirus Infections. Where Does COVID-19 Stand? Viruses. 2020;12(8):07. DOI: 10.3390/v12080861 ABSTRACT: Seven years after the Middle East respiratory syndrome (MERS) outbreak, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) made its first appearance in a food market in Wuhan, China, drawing an entirely new course to our lives. As the virus belongs to the same genus of MERS and SARS, researchers have been trying to draw lessons from previous outbreaks to find a potential cure. Although there were five Phase I human vaccine trials against SARS and MERS, the lack of data in humans provided us with limited benchmarks that could help us design a new vaccine for Coronavirus disease 2019 (COVID-19). In this review, we showcase the similarities in structures of virus components between SARS-CoV, MERS-CoV, and SARS-CoV-2 in areas relevant to vaccine design. Using the ClinicalTrials.gov and World Health Organization (WHO) databases, we shed light on the 16 current approved clinical trials worldwide in search for a COVID-19 vaccine. The different vaccine platforms being tested are Bacillus Calmette-Guerin (BCG) vaccines, DNA and RNA- based vaccines, inactivated vaccines, protein subunits, and viral vectors. By thoroughly analyzing different trials and platforms, we also discuss the advantages and disadvantages of using each type of vaccine and how they can contribute to the design of an adequate vaccine for COVID-19. Studying past efforts invested in conducting vaccine trials for MERS and SARS will provide vital insights regarding the best approach to designing an effective vaccine against COVID-19.
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URL: https://www.ncbi.nlm.nih.gov/pubmed/32784685 DOI: 10.3390/v12080861
4. Baker D, Roberts CAK, Pryce G, et al. COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases. Clin Exp Immunol. 2020;202(2):149-61. DOI: 10.1111/cei.13495 ABSTRACT: Although most autoimmune diseases are considered to be CD4 T cell- or antibody-mediated, many respond to CD20-depleting antibodies that have limited influence on CD4 and plasma cells. This includes rituximab, oblinutuzumab and ofatumumab that are used in cancer, rheumatoid arthritis and off-label in a large number of other autoimmunities and ocrelizumab in multiple sclerosis. Recently, the COVID-19 pandemic created concerns about immunosuppression in autoimmunity, leading to cessation or a delay in immunotherapy treatments. However, based on the known and emerging biology of autoimmunity and COVID-19, it was hypothesised that while B cell depletion should not necessarily expose people to severe SARS-CoV-2-related issues, it may inhibit protective immunity following infection and vaccination. As such, drug-induced B cell subset inhibition, that controls at least some autoimmunities, would not influence innate and CD8 T cell responses, which are central to SARS-CoV-2 elimination, nor the hypercoagulation and innate inflammation causing severe morbidity. This is supported clinically, as the majority of SARS-CoV-2-infected, CD20-depleted people with autoimmunity have recovered. However, protective neutralizing antibody and vaccination responses are predicted to be blunted until naive B cells repopulate, based on B cell repopulation kinetics and vaccination responses, from published rituximab and unpublished ocrelizumab (NCT00676715, NCT02545868) trial data, shown here. This suggests that it may be possible to undertake dose interruption to maintain inflammatory disease control, while allowing effective vaccination against SARS- CoV-29, if and when an effective vaccine is available. URL: https://www.ncbi.nlm.nih.gov/pubmed/32671831 DOI: 10.1111/cei.13495
5. Bartsch SM, O'Shea KJ, Ferguson MC, et al. Vaccine Efficacy Needed for a COVID-19 Coronavirus Vaccine to Prevent or Stop an Epidemic as the Sole Intervention. Am J Prev Med. 2020;59(4):493-503. DOI: 10.1016/j.amepre.2020.06.011 ABSTRACT: INTRODUCTION: Given the continuing COVID-19 pandemic and much of the U.S. implementing social distancing owing to the lack of alternatives, there has been a push to develop a vaccine to eliminate the need for social distancing. METHODS: In 2020, the team developed a computational model of the U.S. simulating the spread of COVID-19 coronavirus and vaccination. RESULTS: Simulation experiments revealed that to prevent an epidemic (reduce the peak by >99%), the vaccine efficacy has to be at least 60% when vaccination coverage is 100% (reproduction number=2.5-3.5). This vaccine efficacy threshold rises to 70% when coverage drops to 75% and up to 80% when coverage drops to 60% when reproduction number is 2.5, rising to 80% when coverage drops to 75% when the reproduction number is 3.5. To extinguish an ongoing epidemic, the vaccine efficacy has to be at least 60% when coverage is 100% and at least 80% when coverage drops to 75% to reduce the peak by 85%-86%, 61%-62%, and 32% when vaccination occurs after 5%, 15%, and 30% of the population, respectively, have already been exposed to COVID-19 coronavirus. A vaccine with an efficacy between 60% and 80% could still obviate the need for other measures under certain circumstances such as much higher, and in some cases, potentially unachievable, vaccination coverages. CONCLUSIONS: This study found that the vaccine has to have an efficacy of at least 70% to prevent an epidemic and of at least 80% to largely extinguish an epidemic without any other measures (e.g., social distancing). URL: https://www.ncbi.nlm.nih.gov/pubmed/32778354 DOI: 10.1016/j.amepre.2020.06.011
6. Bar-Zeev N, Kochhar S. Expecting the unexpected with COVID-19 vaccines. The Lancet Infectious Diseases. 2020. DOI: 10.1016/s1473-3099(20)30870-7 DOI: 10.1016/s1473-3099(20)30870-7
7. Bennet BM, Wolf J, Laureano R, et al. Review of Current Vaccine Development Strategies to Prevent Coronavirus Disease 2019 (COVID-19). Toxicol Pathol. 2020;48(7):800-9. DOI: 10.1177/0192623320959090 ABSTRACT: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak that started in Wuhan, China, in 2019 resulted in a pandemic not seen for a century, and there is an urgent need to develop safe and efficacious vaccines. The scientific community has made tremendous efforts to understand the disease, and unparalleled efforts are ongoing to develop vaccines and treatments. Toxicologists and pathologists are involved in these efforts to test the efficacy and safety of vaccine candidates. Presently, there are several SARS-CoV-2 vaccines in clinical trials, and the pace of vaccine development has been highly accelerated to meet the urgent need. By 2021, efficacy and safety data from clinical trials are
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expected, and potentially a vaccine will be available for those most at risk. This review focuses on the ongoing SARS-CoV-2 vaccine development efforts with emphasis on the nonclinical safety assessment and discusses emerging preliminary data from nonclinical and clinical studies. It also provides a brief overview on vaccines for other coronaviruses, since experience gained from these can be useful in the development of SARS-CoV-2 vaccines. This review will also explain why, despite this unprecedented pace of vaccine development, rigorous standards are in place to ensure nonclinical and clinical safety and efficacy. [Box: see text]. URL: https://www.ncbi.nlm.nih.gov/pubmed/32926660 DOI: 10.1177/0192623320959090
8. Billon-Denis E, Tournier JN. [COVID-19 and vaccination: a global disruption]. Med Sci (Paris). 2020;36(11):1034-7. DOI: 10.1051/medsci/2020203 ABSTRACT: Coronavirus disease (COVID)-19 is an emerging pandemic infection whose significant ability to spread in a naive population is well established. The first response of states to the COVID-19 outbreak was to impose lock-down and social barrier measures, such as wearing a surgical mask or social distancing. One of the consequences of this pandemic in terms of public health was the suspension or slowdown of infant vaccination campaigns, in almost all countries. The indirect effects of COVID-19 may therefore weigh on mortality from measles and polio in developing countries. In this pandemic chaos, the only hope lies in the rapid development of an effective vaccine against severe acute respiratory syndrome- coronavirus-2 (SARS-CoV-2). However, acceptance of this vaccine has not yet been won, as beyond the many unknowns that will inevitably weigh around such rapid development, skepticism among vaccine hesitants is growing. URL: https://www.ncbi.nlm.nih.gov/pubmed/33151866 DOI: 10.1051/medsci/2020203
9. Chauhan G, Madou MJ, Kalra S, et al. Nanotechnology for COVID-19: Therapeutics and Vaccine Research. ACS Nano. 2020;14(7):7760-82. DOI: 10.1021/acsnano.0c04006 ABSTRACT: The current global health threat by the novel coronavirus disease 2019 (COVID-19) requires an urgent deployment of advanced therapeutic options available. The role of nanotechnology is highly relevant to counter this "virus" nano enemy. Nano intervention is discussed in terms of designing effective nanocarriers to counter the conventional limitations of antiviral and biological therapeutics. This strategy directs the safe and effective delivery of available therapeutic options using engineered nanocarriers, blocking the initial interactions of viral spike glycoprotein with host cell surface receptors, and disruption of virion construction. Controlling and eliminating the spread and reoccurrence of this pandemic demands a safe and effective vaccine strategy. Nanocarriers have potential to design risk-free and effective immunization strategies for severe acute respiratory syndrome coronavirus 2 vaccine candidates such as protein constructs and nucleic acids. We discuss recent as well as ongoing nanotechnology-based therapeutic and prophylactic strategies to fight against this pandemic, outlining the key areas for nanoscientists to step in. URL: https://www.ncbi.nlm.nih.gov/pubmed/32571007 DOI: 10.1021/acsnano.0c04006
10. Che Y, Liu X, Pu Y, et al. Randomized, double-blinded and placebo-controlled phase II trial of an inactivated SARS- CoV-2 vaccine in healthy adults. Clin Infect Dis. 2020. DOI: 10.1093/cid/ciaa1703 ABSTRACT: BACKGROUND: We evaluated an inactivated SARS-CoV-2 vaccine for immunogenicity and safety in adults aged 18-59 years. METHODS: In this randomized, double-blinded and controlled trial, healthy adults received a medium (MD) or a high dose (HD) of the vaccine at an interval of either 14 days or 28 days. Neutralizing antibody (NAb) and anti-S and anti-N antibodies were detected at different times, and adverse reactions were monitored for 28 days after full immunization. RESULTS: A total of 742 adults were enrolled in the immunogenicity and safety analysis. Among subjects in the 0, 14 procedure, the seroconversion rates of NAb in MD and HD groups were 89% and 96% with GMTs of 23 and 30, respectively, at day 14 and 92% and 96% with GMTs of 19 and 21, respectively at day 28 after immunization. Anti -S antibodies had GMTs of 1883 and 2370 in MD and 2295 and 2432 in HD group. Anti -N antibodies had GMTs of 387 and 434 in MD group and 342 and 380 in HD group. Among subjects in the 0, 28 procedure, seroconversion rates for NAb at both doses were both 95% with GMTs of 19 at day 28 after immunization. Anti-S antibodies had GMTs of 937 and 929 for MD and HD group, and anti- N antibodies had GMTs of 570 and 494 for MD and HD group, respectively. No serious adverse events were observed during the study period. CONCLUSION: Adults vaccinated with inactivated SARS-CoV-2 vaccine had NAb as well as anti-S/N antibody, and had a low rate of adverse reactions. CLINICAL TRIALS REGISTRATION: NCT04412538. URL: https://www.ncbi.nlm.nih.gov/pubmed/33165503 DOI: 10.1093/cid/ciaa1703
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11. Choi W, Shim E. Optimal strategies for vaccination and social distancing in a game-theoretic epidemiologic model. J Theor Biol. 2020;505:110422. DOI: 10.1016/j.jtbi.2020.110422 ABSTRACT: For various infectious diseases, vaccination has become a major intervention strategy. However, the importance of social distancing has recently been highlighted during the ongoing COVID-19 pandemic. In the absence of vaccination, or when vaccine efficacy is poor, social distancing may help to curb the spread of new virus strains. However, both vaccination and social distancing are associated with various costs. It is critical to consider these costs in addition to the benefits of these strategies when determining the optimal rates of application of control strategies. We developed a game-theoretic epidemiological model that considers vaccination and social distancing under the assumption that individuals pursue the maximization of payoffs. By using this model, we identified the individually optimal strategy based on the Nash strategy when both strategies are available and when only one strategy is available. Furthermore, we determined the relative costs of control strategies at which individuals preferentially adopt vaccination over social distancing (or vice versa). URL: https://www.ncbi.nlm.nih.gov/pubmed/32717195 DOI: 10.1016/j.jtbi.2020.110422
12. Chukwudozie OS, Chukwuanukwu RC, Iroanya OO, et al. Attenuated Subcomponent Vaccine Design Targeting the SARS-CoV-2 Nucleocapsid Phosphoprotein RNA Binding Domain: In Silico Analysis. J Immunol Res. 2020;2020:2837670. DOI: 10.1155/2020/2837670 ABSTRACT: The novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) has previously never been identified with humans, thereby creating devastation in public health. The need for an effective vaccine to curb this pandemic cannot be overemphasized. In view of this, we designed a subcomponent antigenic peptide vaccine targeting the N-terminal (NT) and C-terminal (CT) RNA binding domains of the nucleocapsid protein that aid in viral replication. Promising antigenic B cell and T cell epitopes were predicted using computational pipelines. The peptides "RIRGGDGKMKDL" and "AFGRRGPEQTQGNFG" were the B cell linear epitopes with good antigenic index and nonallergenic property. Two CD8(+) and Three CD4(+) T cell epitopes were also selected considering their safe immunogenic profiling such as allergenicity, antigen level conservancy, antigenicity, peptide toxicity, and putative restrictions to a number of MHC-I and MHC-II alleles. With these selected epitopes, a nonallergenic chimeric peptide vaccine incapable of inducing a type II hypersensitivity reaction was constructed. The molecular interaction between the Toll-like receptor-5 (TLR5) which was triggered by the vaccine was analyzed by molecular docking and scrutinized using dynamics simulation. Finally, in silico cloning was performed to ensure the expression and translation efficiency of the vaccine, utilizing the pET-28a vector. This research, therefore, provides a guide for experimental investigation and validation. URL: https://www.ncbi.nlm.nih.gov/pubmed/32964056 DOI: 10.1155/2020/2837670
13. Chung YH, Beiss V, Fiering SN, et al. COVID-19 Vaccine Frontrunners and Their Nanotechnology Design. ACS Nano. 2020;14(10):12522-37. DOI: 10.1021/acsnano.0c07197 ABSTRACT: Humanity is experiencing a catastrophic pandemic. SARS-CoV-2 has spread globally to cause significant morbidity and mortality, and there still remain unknowns about the biology and pathology of the virus. Even with testing, tracing, and social distancing, many countries are struggling to contain SARS-CoV-2. COVID-19 will only be suppressible when herd immunity develops, either because of an effective vaccine or if the population has been infected and is resistant to reinfection. There is virtually no chance of a return to pre-COVID-19 societal behavior until there is an effective vaccine. Concerted efforts by physicians, academic laboratories, and companies around the world have improved detection and treatment and made promising early steps, developing many vaccine candidates at a pace that has been unmatched for prior diseases. As of August 11, 2020, 28 of these companies have advanced into clinical trials with Moderna, CanSino, the University of Oxford, BioNTech, Sinovac, Sinopharm, Anhui Zhifei Longcom, Inovio, Novavax, Vaxine, Zydus Cadila, Institute of Medical Biology, and the Gamaleya Research Institute having moved beyond their initial safety and immunogenicity studies. This review analyzes these frontrunners in the vaccine development space and delves into their posted results while highlighting the role of the nanotechnologies applied by all the vaccine developers. URL: https://www.ncbi.nlm.nih.gov/pubmed/33034449 DOI: 10.1021/acsnano.0c07197
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14. Cioffi A. Coronavirus Disease 2019: Is Everything Lawful to Create an Effective Vaccine? J Infect Dis. 2020;222(1):169. DOI: 10.1093/infdis/jiaa216 URL: https://www.ncbi.nlm.nih.gov/pubmed/32348489 DOI: 10.1093/infdis/jiaa216
15. Dean NE, Pastore YPA, Madewell ZJ, et al. Ensemble forecast modeling for the design of COVID-19 vaccine efficacy trials. Vaccine. 2020;38(46):7213-6. DOI: 10.1016/j.vaccine.2020.09.031 ABSTRACT: To rapidly evaluate the safety and efficacy of COVID-19 vaccine candidates, prioritizing vaccine trial sites in areas with high expected disease incidence can speed endpoint accrual and shorten trial duration. Mathematical and statistical forecast models can inform the process of site selection, integrating available data sources and facilitating comparisons across locations. We recommend the use of ensemble forecast modeling - combining projections from independent modeling groups - to guide investigators identifying suitable sites for COVID-19 vaccine efficacy trials. We describe an appropriate structure for this process, including minimum requirements, suggested output, and a user-friendly tool for displaying results. Importantly, we advise that this process be repeated regularly throughout the trial, to inform decisions about enrolling new participants at existing sites with waning incidence versus adding entirely new sites. These types of data-driven models can support the implementation of flexible efficacy trials tailored to the outbreak setting. URL: https://www.ncbi.nlm.nih.gov/pubmed/33012602 DOI: 10.1016/j.vaccine.2020.09.031
16. Dearlove B, Lewitus E, Bai H, et al. A SARS-CoV-2 vaccine candidate would likely match all currently circulating variants. Proc Natl Acad Sci U S A. 2020;117(38):23652-62. DOI: 10.1073/pnas.2008281117 ABSTRACT: The magnitude of the COVID-19 pandemic underscores the urgency for a safe and effective vaccine. Many vaccine candidates focus on the Spike protein, as it is targeted by neutralizing antibodies and plays a key role in vi ral entry. Here we investigate the diversity seen in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequences and compare it to the sequence on which most vaccine candidates are based. Using 18,514 sequences, we perform phylogenetic, population genetics, and structural bioinformatics analyses. We find limited diversity across SARS-CoV-2 genomes: Only 11 sites show polymorphisms in >5% of sequences; yet two mutations, including the D614G mutation in Spike, have already become consensus. Because SARS-CoV-2 is being transmitted more rapidly than it evolves, the viral population is becoming more homogeneous, with a median of seven nucleotide substitutions between genomes. There is evidence of purifying selection but little evidence of diversifying selection, with substitution rates comparable across structural versus nonstructural genes. Finally, the Wuhan-Hu-1 reference sequence for the Spike protein, which is the basis for different vaccine candidates, matches optimized vaccine inserts, being identical to an ancestral sequence and one mutation away from the consensus. While the rapid spread of the D614G mutation warrants further study, our results indicate that drift and bottleneck events can explain the minimal diversity found among SARS-CoV-2 sequences. These findings suggest that a single vaccine candidate should be efficacious against currently circulating lineages. URL: https://www.ncbi.nlm.nih.gov/pubmed/32868447 DOI: 10.1073/pnas.2008281117
17. Folegatti PM, Ewer KJ, Aley PK, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV- 2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. The Lancet. 2020;396(10249):467-78. DOI: 10.1016/s0140-6736(20)31604-4 DOI: 10.1016/s0140-6736(20)31604-4
18. Galili U. Amplifying immunogenicity of prospective Covid-19 vaccines by glycoengineering the coronavirus glycan- shield to present alpha-gal epitopes. Vaccine. 2020;38(42):6487-99. DOI: 10.1016/j.vaccine.2020.08.032 ABSTRACT: The many carbohydrate chains on Covid-19 coronavirus SARS-CoV-2 and its S-protein form a glycan-shield that masks antigenic peptides and decreases uptake of inactivated virus or S-protein vaccines by APC. Studies on inactivated influenza virus and recombinant gp120 of HIV vaccines indicate that glycoengineering of glycan-shields to present alpha-gal epitopes (Galalpha1-3Galbeta1-4GlcNAc-R) enables harnessing of the natural anti-Gal antibody for amplifying vaccine efficacy, as evaluated in mice producing anti-Gal. The alpha-gal epitope is the ligand for the natural anti-Gal antibody which constitutes ~1% of immunoglobulins in humans. Upon administration of vaccines presenting alpha-gal epitopes, anti-Gal binds to these epitopes at the vaccination site and forms immune complexes with the vaccines. These immune complexes are targeted for extensive uptake by APC as a result of binding of the Fc portion of immunocomplexed anti -Gal to Fc receptors on APC. This anti-Gal mediated effective uptake of vaccines by APC results in 10-200-fold higher anti-viral
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immune response and in 8-fold higher survival rate following challenge with a lethal dose of live influenza virus, than same vaccines lacking alpha-gal epitopes. It is suggested that glycoengineering of carbohydrate chains on the glycan-shield of inactivated SARS-CoV-2 or on S-protein vaccines, for presenting alpha-gal epitopes, will have similar amplifying effects on vaccine efficacy. alpha-Gal epitope synthesis on coronavirus vaccines can be achieved with recombinant alpha1,3galactosyltransferase, replication of the virus in cells with high alpha1,3galactosyltransferase activity as a result of stable transfection of cells with several copies of the alpha1,3galactosyltransferase gene (GGTA1), or by transduction of host cells with replication defective adenovirus containing this gene. In addition, recombinant S-protein presenting multiple alpha-gal epitopes on the glycan-shield may be produced in glycoengineered yeast or bacteria expression systems containing the corresponding glycosyltransferases. Prospective Covid-19 vaccines presenting alpha-gal epitopes may provide better protection than vaccines lacking this epitope because of increased uptake by APC. URL: https://www.ncbi.nlm.nih.gov/pubmed/32907757 DOI: 10.1016/j.vaccine.2020.08.032
19. Glasper A. The quest to find an effective vaccine for COVID-19. Br J Nurs. 2020;29(11):644-6. DOI: 10.12968/bjon.2020.29.11.644 ABSTRACT: Professor Alan Glasper, from the University of Southampton, delves into history and discusses the international quest to develop an effective vaccine to tackle COVID-19. URL: https://www.ncbi.nlm.nih.gov/pubmed/32516041 DOI: 10.12968/bjon.2020.29.11.644
20. Grech V, Borg M. Influenza vaccination in the COVID-19 era. Early Hum Dev. 2020;148:105116. DOI: 10.1016/j.earlhumdev.2020.105116 ABSTRACT: Influenza spreads globally annually with significant paediatric and adult attack rates and considerable morbidity, mortality and the exacerbation of extant chronic disease. In the northern and southern hemispheres, outbreaks occur mainly in the respective winter seasons. Influenza vaccination is available but only partially effective. In the absence of a vaccine, in winter, novel coronavirus COVID-19 will also circulate in parallel with seasonal influenza. Thus far it appears that with the current strains of these two viruses, the clinical outcome of co-infection is not significantly worse than infection with COVID-19 alone. However, several strains of influenza circulate, including strains still to come. Similarly, COVID-19 has several strains, with probably more to come. This paper discusses these issues and estimates ideal minimum influenza vaccination coverage based on an estimated influenza Basic Reproduction Number (R0) of 0.9-2.1 so as to obtain herd immunity or approach it. There is a strong argument for attempting near universal population coverage with the annual influenza vaccine leading up to next winter. URL: https://www.ncbi.nlm.nih.gov/pubmed/32604011 DOI: 10.1016/j.earlhumdev.2020.105116
21. Gupta T, Gupta SK. Potential adjuvants for the development of a SARS-CoV-2 vaccine based on experimental results from similar coronaviruses. Int Immunopharmacol. 2020;86:106717. DOI: 10.1016/j.intimp.2020.106717 ABSTRACT: The extensive efforts around the globe are being made to develop a suitable vaccine against COVID-19 (Coronavirus Disease-19) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2). An effective vaccine should be able to induce high titers of neutralizing antibodies to prevent the virus from attaching to the host cell receptors. However, to elicit the protective levels of antibodies, a vaccine may require multiple doses or assistance from other immunostimulatory molecules. Further, the vaccine should be able to induce protective levels of antibodies rapidly with the least amount of antigen used. This decreases the cost of a vaccine and makes it affordable. As the pandemic has hit most countries across the globe, there will be an overwhelming demand for the vaccine in a quick time. Incorporating a suitable adjuvant in a SARS-CoV-2 vaccine may address these requirements. This review paper will discuss the experimental results of the adjuvanted vaccine studies with similar coronaviruses (CoVs) which might be useful to select an appropriate adjuvant for a vaccine against rapidly emergingSARS-CoV-2. We also discuss the current progress in the development of adjuvanted vaccines against the disease. URL: https://www.ncbi.nlm.nih.gov/pubmed/32585611 DOI: 10.1016/j.intimp.2020.106717
22. Hassan AO, Kafai NM, Dmitriev IP, et al. A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2. Cell. 2020;183(1):169-84 e13. DOI: 10.1016/j.cell.2020.08.026
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ABSTRACT: The coronavirus disease 2019 pandemic has made deployment of an effective vaccine a global health priority. We evaluated the protective activity of a chimpanzee adenovirus-vectored vaccine encoding a prefusion stabilized spike protein (ChAd-SARS-CoV-2-S) in challenge studies with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mice expressing the human angiotensin-converting enzyme 2 receptor. Intramuscular dosing of ChAd-SARS-CoV-2-S induces robust systemic humoral and cell-mediated immune responses and protects against lung infection, inflammation, and pathology but does not confer sterilizing immunity, as evidenced by detection of viral RNA and induction of anti- nucleoprotein antibodies after SARS-CoV-2 challenge. In contrast, a single intranasal dose of ChAd-SARS-CoV-2-S induces high levels of neutralizing antibodies, promotes systemic and mucosal immunoglobulin A (IgA) and T cell responses, and almost entirely prevents SARS-CoV-2 infection in both the upper and lower respiratory tracts. Intranasal administration of ChAd-SARS-CoV-2-S is a candidate for preventing SARS-CoV-2 infection and transmission and curtailing pandemic spread. URL: https://www.ncbi.nlm.nih.gov/pubmed/32931734 DOI: 10.1016/j.cell.2020.08.026
23. Hodgson SH, Mansatta K, Mallett G, et al. What defines an efficacious COVID-19 vaccine? A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2. The Lancet Infectious Diseases. 2020. DOI: http://dx.doi.org/10.1016/S1473-3099%2820%2930773-8 ABSTRACT: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 1 million deaths in the first 6 months of the pandemic and huge economic and social upheaval internationally. An effi cacious vaccine is essential to prevent further morbidity and mortality. Although some countries might deploy COVID-19 vaccines on the strength of safety and immunogenicity data alone, the goal of vaccine development is to gain direct evidence of vaccine efficacy in protecting humans against SARS-CoV-2 infection and COVID-19 so that manufacture of efficacious vaccines can be selectively upscaled. A candidate vaccine against SARS-CoV-2 might act against infection, disease, or transmission, and a vaccine capable of reducing any of these elements could contribute to disease control. However, the most important efficacy endpoint, protection against severe disease and death, is difficult to assess in phase 3 clinical trials. In this Review, we explore the challenges in assessing the efficacy of candidate SARS-CoV-2 vaccines, discuss the caveats needed to interpret reported efficacy endpoints, and provide insight into answering the seemingly simple question, "Does this COVID-19 vaccine work?" Copyright © 2020 Elsevier Ltd URL: http://www.journals.elsevier.com/the-lancet-infectious-diseases DOI: http://dx.doi.org/10.1016/S1473-3099%2820%2930773-8
24. Huang SW, Tai CH, Hsu YM, et al. Assessing the application of a pseudovirus system for emerging SARS-CoV-2 and re- emerging avian influenza virus H5 subtypes in vaccine development. Biomed J. 2020;43(4):375-87. DOI: 10.1016/j.bj.2020.06.003 ABSTRACT: BACKGROUND: Highly pathogenic emerging and re-emerging viruses continuously threaten lives worldwide. In order to provide prophylactic prevention from the emerging and re-emerging viruses, vaccine is suggested as the most efficient way to prevent individuals from the threat of viral infection. Nonetheless, the highly pathogenic viruses need to be handled in a high level of biosafety containment, which hinders vaccine development. To shorten the timeframe of vaccine development, the pseudovirus system has been widely applied to examine vaccine efficacy or immunogenicity in the emerging and re-emerging viruses. METHODS: We developed pseudovirus systems for emerging SARS coronavirus 2 (SARS- CoV-2) and re-emerging avian influenza virus H5 subtypes which can be handled in the biosafety level 2 facility. Through the generated pseudovirus of SARS-CoV-2 and avian influenza virus H5 subtypes, we successfully established a neutralization assay to quantify the neutralizing activity of antisera against the viruses. RESULTS: The result of re-emerging avian influenza virus H5Nx pseudoviruses provided valuable information for antigenic evolution and immunogenicity analysis in vaccine candidate selection. Together, our study assessed the potency of pseudovirus systems in vaccine efficacy, antigenic analysis, and immunogenicity in the vaccine development of emerging and re-emerging viruses. CONCLUSION: Instead of handling live highly pathogenic viruses in a high biosafety level facility, using pseudovirus systems would speed up the process of vaccine development to provide community protection against emerging and re-emerging viral diseases with high pathogenicity. URL: https://www.ncbi.nlm.nih.gov/pubmed/32611537 DOI: 10.1016/j.bj.2020.06.003
25. Huang W, Liu T, Feng G, et al. [Progress in possible effects of BCG vaccine on the prevention of SARS-CoV-2 infection: An update]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2020;36(11):1044-8.
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ABSTRACT: The research and development of the coronavirus disease 2019 (COVID-19) vaccine is being carried out globally. Although vaccine research and development technology has made great progress, the possibility of obtaining a safe and effective vaccine that can control the global epidemic in a short period of time is still low due to the antibody-dependent enhancement effect (ADE) of the vaccine and the mutation of the virus. In the absence of specific treatment for COVID-19, finding other alternative protection schemes has become another treatment idea. Epidemiological studies have found that, in this COVID-19 epidemic, countries with long-term Bacillus Calmette-Guerin (BCG) vaccination policies have relatively less cases and lower mortality rates than countries without relevant policies. This phenomenon may be related to the "training immunity" effect of BCG. In order to further clarify the preventive and protective effects of BCG vaccine on SARS-CoV-2 infection, a number of clinical trials are underway. URL: https://www.ncbi.nlm.nih.gov/pubmed/33210600
26. Jain N, Shankar U, Majee P, et al. Scrutinizing the SARS-CoV-2 protein information for designing an effective vaccine encompassing both the T-cell and B-cell epitopes. Infect Genet Evol. 2020;87(104648):104648. DOI: 10.1016/j.meegid.2020.104648 ABSTRACT: Novel SARS coronavirus (SARS-CoV-2) has caused a pandemic condition worldwide. It has been declared as a public health emergency of international concern by WHO in a very short span of time. The community transmission of this highly infectious virus has severely affected various parts of China, Italy, Spain, India, and USA, among others. The prophylactic solution against SARS-CoV-2 infection is challenging due to the high mutation rate of its RNA genome. Herein, we exploited a next-generation vaccinology approach to construct a multi-epitope vaccine candidate against SARS-CoV-2 that is predicted to have high antigenicity, safety, and efficacy to combat this deadly infectious agent. The whole proteome was scrutinized for the screening of highly conserved, antigenic, non-allergen, and non-toxic epitopes having high population coverage that can elicit both humoral and cellular mediated immune response against COVID-19 infection. These epitopes along with four different adjuvants, were utilized to construct a multi-epitope-vaccine candidate that can generate strong immunological memory response having high efficacy in humans. Various physiochemical analyses revealed the formation of a stable vaccine product having a high propensity to form a protective solution against the detrimental SARS-CoV-2 strain with high efficacy. The vaccine candidate interacted with immunological receptor TLR3 with a high affinity depicting the generation of innate immunity. Further, the codon optimization and in silico expression show the plausibility of the high expression and easy purification of the vaccine product. Thus, this present study provides an initial platform for the rapid generation of an efficacious protective vaccine for combating COVID-19. URL: https://www.ncbi.nlm.nih.gov/pubmed/33264668 DOI: 10.1016/j.meegid.2020.104648
27. Jamrozik E, Selgelid MJ. COVID-19 human challenge studies: ethical issues. Lancet Infect Dis. 2020;20(8):e198-e203. DOI: 10.1016/S1473-3099(20)30438-2 ABSTRACT: COVID-19 poses an extraordinary threat to global public health and an effective vaccine could provide a key means of overcoming this crisis. Human challenge studies involve the intentional infection of research participants and can accelerate or improve vaccine development by rapidly providing estimates of vaccine safety and efficacy. Human challenge studies of low virulence coronaviruses have been done in the past and human challenge studies with severe acute respiratory syndrome coronavirus 2 have been proposed. These studies of coronaviruses could provide considerable benefits to public health; for instance, by improving and accelerating vaccine development. However, human challenge studies of severe acute respiratory syndrome coronavirus 2 in particular might be controversial, in part, for ethical reasons. The ethical issues raised by such studies thus warrant early consideration involving, for example, broad consultation with the community. This Personal View provides preliminary analyses of relevant ethical considerations regarding human challenge studies of severe acute respiratory syndrome coronavirus 2, including the potential benefits to public health and to participants, the risks and uncertainty for participants, and the third-party risks (ie, to research staff and the wider community). We argue that these human challenge studies can reasonably be considered ethically acceptable insofar as such studies are accepted internationally and by the communities in which they are done, can realistically be expected to accelerate or improve vaccine development, have considerable potential to directly benefit participants, are designed to limit and minimise risks to participants, and are done with strict infection control measures to limit and reduce third-party risks. URL: https://www.ncbi.nlm.nih.gov/pubmed/32479747 DOI: 10.1016/S1473-3099(20)30438-2
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28. Jeyanathan M, Afkhami S, Smaill F, et al. Immunological considerations for COVID-19 vaccine strategies. Nat Rev Immunol. 2020;20(10):615-32. DOI: 10.1038/s41577-020-00434-6 ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the most formidable challenge to humanity in a century. It is widely believed that prepandemic normalcy will never return until a safe and effective vaccine strategy becomes available and a global vaccination programme is implemented successfully. Here, we discuss the immunological principles that need to be taken into consideration in the development of COVID-19 vaccine strategies. On the basis of these principles, we examine the current COVID-19 vaccine candidates, their strengths and potential shortfalls, and make inferences about their chances of success. Finally, we discuss the scientific and practical challenges that will be faced in the process of developing a successful vaccine and the ways in which COVID-19 vaccine strategies may evolve over the next few years. URL: https://www.ncbi.nlm.nih.gov/pubmed/32887954 DOI: 10.1038/s41577-020-00434-6
29. Jiang Z, Wang X, Xia J. Considerations on the clinical development of COVID-19 vaccine from trial design perspectives. Hum Vaccin Immunother. 2020:1-5. DOI: 10.1080/21645515.2020.1815489 ABSTRACT: COVID-19 has become a global pandemic, and an effective vaccine is needed. During the outbreak, the urgency for developing candidate vaccines has brought distinct challenges to clinical development. An efficacy trial, which measures whether the vaccine reduces the incidence of disease, is ordinarily required to fully evaluate vaccine efficacy. However, emergency use may be possible if promising immunogenicity results are observed. A ring vaccination trial, which recruits subjects connected to a known case either socially or geographically, is a solution to evaluate vaccine efficacy and control the spread of the disease simultaneously although its conduct is challenging. Nevertheless, when COVID-19 becomes a recurrent epidemic, an 'individual-level' efficacy trial is preferred. Innovative statistical designs, including seamless design, platform trial, master protocol design, are helpful to accelerate clinical development. A seamless Phase I/II design has been applied in multiple COVID-19 vaccine studies to date. However, Phase II/III design should be done very carefully. The control of type I error, maintaining trial blinding and statistical methods leading to unbiased estimates should be pre-specified in the clinical protocol. A Data Safety Monitoring Board is especially important, given the need to assure an adequate level of safety when society want a safe and effective vaccine. URL: https://www.ncbi.nlm.nih.gov/pubmed/32991223 DOI: 10.1080/21645515.2020.1815489
30. Kames J, Holcomb DD, Kimchi O, et al. Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design. Sci Rep. 2020;10(1):15643. DOI: 10.1038/s41598-020-72533-2 ABSTRACT: As the SARS-CoV-2 pandemic is rapidly progressing, the need for the development of an effective vaccine is critical. A promising approach for vaccine development is to generate, through codon pair deoptimization, an attenuated virus. This approach carries the advantage that it only requires limited knowledge specific to the virus in question, other than its genome sequence. Therefore, it is well suited for emerging viruses, for which we may not have extensive data. We performed comprehensive in silico analyses of several features of SARS-CoV-2 genomic sequence (e.g., codon usage, codon pair usage, dinucleotide/junction dinucleotide usage, RNA structure around the frameshift region) in comparison with other members of the coronaviridae family of viruses, the overall human genome, and the transcriptome of specific human tissues such as lung, which are primarily targeted by the virus. Our analysis identified the spike (S) and nucleocapsid (N) proteins as promising targets for deoptimization and suggests a roadmap for SARS-CoV-2 vaccine development, which can be generalizable to other viruses. URL: https://www.ncbi.nlm.nih.gov/pubmed/32973171 DOI: 10.1038/s41598-020-72533-2
31. Kaur SP, Gupta V. COVID-19 Vaccine: A comprehensive status report. Virus Res. 2020;288:198114. DOI: 10.1016/j.virusres.2020.198114 ABSTRACT: The current COVID-19 pandemic has urged the scientific community internationally to find answers in terms of therapeutics and vaccines to control SARS-CoV-2. Published investigations mostly on SARS-CoV and to some extent on MERS has taught lessons on vaccination strategies to this novel coronavirus. This is attributed to the fact that SARS-CoV-2 uses the same receptor as SARS-CoV on the host cell i.e. human Angiotensin Converting Enzyme 2 (hACE2) and is approximately 79% similar genetically to SARS-CoV. Though the efforts on COVID-19 vaccines started very early, initially in China, as soon as the outbreak of novel coronavirus erupted and then world-over as the disease was declared a pandemic by WHO. But we will not be having an effective COVID-19 vaccine before September, 2020 as per very optimistic estimates.
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This is because a successful COVID-19 vaccine will require a cautious validation of efficacy and adverse reactivity as the target vaccinee population include high-risk individuals over the age of 60, particularly those with chronic co-morbid conditions, frontline healthcare workers and those involved in essentials industries. Various platforms for vaccine development are available namely: virus vectored vaccines, protein subunit vaccines, genetic vaccines, and monoclonal antibodies for passive immunization which are under evaluations for SARS-CoV-2, with each having discrete benefits and hindrances. The COVID-19 pandemic which probably is the most devastating one in the last 100 years after Spanish flu mandates the speedy evaluation of the multiple approaches for competence to elicit protective immunity and safety to curtail unwanted immune-potentiation which plays an important role in the pathogenesis of this virus. This review is aimed at providing an overview of the efforts dedicated to an effective vaccine for this novel coronavirus which has crippled the world in terms of economy, human health and life. URL: https://www.ncbi.nlm.nih.gov/pubmed/32800805 DOI: 10.1016/j.virusres.2020.198114
32. Keech C, Albert G, Cho I, et al. Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. N Engl J Med. 2020;383(24):2320-32. DOI: 10.1056/NEJMoa2026920 ABSTRACT: BACKGROUND: NVX-CoV2373 is a recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant. METHODS: We initiated a randomized, placebo-controlled, phase 1-2 trial to evaluate the safety and immunogenicity of the rSARS-CoV- 2 vaccine (in 5-mug and 25-mug doses, with or without Matrix-M1 adjuvant, and with observers unaware of trial-group assignments) in 131 healthy adults. In phase 1, vaccination comprised two intramuscular injections, 21 days apart. The primary outcomes were reactogenicity; laboratory values (serum chemistry and hematology), according to Food and Drug Administration toxicity scoring, to assess safety; and IgG anti-spike protein response (in enzyme-linked immunosorbent assay [ELISA] units). Secondary outcomes included unsolicited adverse events, wild-type virus neutralization (microneutralization assay), and T-cell responses (cytokine staining). IgG and microneutralization assay results were compared with 32 (IgG) and 29 (neutralization) convalescent serum samples from patients with Covid-19, most of whom were symptomatic. We performed a primary analysis at day 35. RESULTS: After randomization, 83 participants were assigned to receive the vaccine with adjuvant and 25 without adjuvant, and 23 participants were assigned to receive placebo. No serious adverse events were noted. Reactogenicity was absent or mild in the majority of participants, more common with adjuvant, and of short duration (mean,
33. Khalaj-Hedayati A. Protective Immunity against SARS Subunit Vaccine Candidates Based on Spike Protein: Lessons for Coronavirus Vaccine Development. J Immunol Res. 2020;2020:7201752. DOI: 10.1155/2020/7201752 ABSTRACT: The recent outbreak of the novel coronavirus disease, COVID-19, has highlighted the threat that highly pathogenic coronaviruses have on global health security and the imminent need to design an effective vaccine for prevention purposes. Although several attempts have been made to develop vaccines against human coronavirus infections since the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in 2003, there is no available licensed vaccine yet. A better understanding of previous coronavirus vaccine studies may help to design a vaccine for the newly emerged virus, SARS-CoV-2, that may also cover other pathogenic coronaviruses as a potentially universal vaccine. In general, coronavirus spike protein is the major antigen for the vaccine design as it can induce neutralizing antibodies and protective immunity. By considering the high genetic similarity between SARS-CoV and SARS-CoV-2, here, protective immunity against SARS-CoV spike subunit vaccine candidates in animal models has been reviewed to gain advances that can facilitate coronavirus vaccine development in the near future. URL: https://www.ncbi.nlm.nih.gov/pubmed/32695833 DOI: 10.1155/2020/7201752
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34. Knoll MD, Wonodi C. Oxford-AstraZeneca COVID-19 vaccine efficacy. Lancet. 2020. DOI: 10.1016/S0140- 6736(20)32623-4 URL: https://www.ncbi.nlm.nih.gov/pubmed/33306990 DOI: 10.1016/S0140-6736(20)32623-4
35. Ledford H. US authorization of first COVID vaccine marks new phase in safety monitoring. Nature. 2020;588(7838):377-8. DOI: 10.1038/d41586-020-03542-4 DOI: 10.1038/d41586-020-03542-4
36. Lipsitch M, Dean NE. Understanding COVID-19 vaccine efficacy. Science. 2020;370(6518):763-5. DOI: 10.1126/science.abe5938 URL: https://www.ncbi.nlm.nih.gov/pubmed/33087460 DOI: 10.1126/science.abe5938
37. Liu X, Liu C, Liu G, et al. COVID-19: Progress in diagnostics, therapy and vaccination. Theranostics. 2020;10(17):7821- 35. DOI: 10.7150/thno.47987 ABSTRACT: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently become a pandemic. As the sudden emergence and rapid spread of SARS-CoV-2 is endangering global health and the economy, the development of strategies to contain the virus's spread are urgently needed. At present, various diagnostic kits to test for SARS-CoV-2 are available for use to initiate appropriate treatment faster and to limit further spread of the virus. Several drugs have demonstrated in vitro activity against SARS-CoV-2 or potential clinical benefits. In addition, institutions and companies worldwide are working tirelessly to develop treatments and vaccines against COVID- 19. However, no drug or vaccine has yet been specifically approved for COVID-19. Given the urgency of the outbreak, we focus here on recent advances in the diagnostics, treatment, and vaccine development for SARS-CoV-2 infection, helping to guide strategies to address the current COVID-19 pandemic. URL: https://www.ncbi.nlm.nih.gov/pubmed/32685022 DOI: 10.7150/thno.47987
38. Mahase E. Covid-19: Pfizer vaccine efficacy was 52% after first dose and 95% after second dose, paper shows. BMJ. 2020;371:m4826. DOI: 10.1136/bmj.m4826 ABSTRACT: The Pfizer and BioNTech covid-19 vaccine may provide some early protection, starting 12 days after the first dose, the peer reviewed results of a phase III trial have found.The study, published in the New England Journal of Medicine,1 found that vaccine efficacy between the first and second doses was 52% (95% credible interval 29.5% to 68.4%), with 39 cases of covid-19 in the vaccine group and 82 cases in the placebo group.Seven or more days after the second dose, vaccine efficacy then rose to 95% (90.3% to 97.6%), with eight covid-19 cases reported in the vaccine group and 162 cases in the placebo group.The vaccine has so far been approved in Canada … URL: https://www.ncbi.nlm.nih.gov/pubmed/33310706 DOI: 10.1136/bmj.m4826
39. Monrad JT. Ethical considerations for epidemic vaccine trials. J Med Ethics. 2020;46(7):465-9. DOI: 10.1136/medethics-2020-106235 ABSTRACT: Vaccines are a powerful measure to protect the health of individuals and to combat outbreaks such as the COVID-19 pandemic. An ethical dilemma arises when one effective vaccine has been successfully developed against an epidemic disease and researchers seek to test the efficacy of another vaccine for the same pathogen in clinical trials involving human subjects. On the one hand, there are compelling reasons why it would be unethical to trial a novel vaccine when an effective product exists already. First, it is a firm principle of medical ethics that an effective treatment or vaccine should not be withheld from patients if their life may depend on it. Second, since epidemic outbreaks often emerge in settings with less-resourced health systems, there is a pronounced risk that any trial withholding an effective vaccine would disproportionately affect the vulnerable populations that historically have been exploited for biomedical research. Third, clinical trials for novel vaccines may be at odds with efforts to control active outbreaks. On the other hand, it may be justified to conduct a trial for a candidate vaccine if it is expected to have certain advantages compared with the existing product. This essay discusses key factors for comparing vaccines against epi demic pathogens, including immunological, logistical and economic considerations. Alongside a case study of the development of vaccines for Ebola, the essay seeks to
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establish a general framework that should be expanded and populated by immunologists, epidemiologists, economists and bioethicists, and ultimately could be applied to the case of COVID-19 vaccines. URL: https://www.ncbi.nlm.nih.gov/pubmed/32414757 DOI: 10.1136/medethics-2020-106235
40. Mukandavire Z, Nyabadza F, Malunguza NJ, et al. Quantifying early COVID-19 outbreak transmission in South Africa and exploring vaccine efficacy scenarios. PLoS One. 2020;15(7):e0236003. DOI: 10.1371/journal.pone.0236003 ABSTRACT: The emergence and fast global spread of COVID-19 has presented one of the greatest public health challenges in modern times with no proven cure or vaccine. Africa is still early in this epidemic, therefore the extent of disease severity is not yet clear. We used a mathematical model to fit to the observed cases of COVID-19 in South Africa to estimate the basic reproductive number and critical vaccination coverage to control the disease for different hypothetical vaccine efficacy scenarios. We also estimated the percentage reduction in effective contacts due to the social distancing measures implemented. Early model estimates show that COVID-19 outbreak in South Africa had a basic reproductive number of 2.95 (95% credible interval [CrI] 2.83-3.33). A vaccine with 70% efficacy had the capacity to contain COVID-19 outbreak but at very higher vaccination coverage 94.44% (95% Crl 92.44-99.92%) with a vaccine of 100% efficacy requiring 66.10% (95% Crl 64.72-69.95%) coverage. Social distancing measures put in place have so far reduced the number of social contacts by 80.31% (95% Crl 79.76-80.85%). These findings suggest that a highly efficacious vaccine would have been required to contain COVID-19 in South Africa. Therefore, the current social distancing measures to reduce contacts will remain key in controlling the infection in the absence of vaccines and other therapeutics. URL: https://www.ncbi.nlm.nih.gov/pubmed/32706790 DOI: 10.1371/journal.pone.0236003
41. Oliveira SC, de Magalhaes MTQ, Homan EJ. Immunoinformatic Analysis of SARS-CoV-2 Nucleocapsid Protein and Identification of COVID-19 Vaccine Targets. Front Immunol. 2020;11:587615. DOI: 10.3389/fimmu.2020.587615 ABSTRACT: COVID-19 is a worldwide emergency; therefore, there is a critical need for foundational knowledge about B and T cell responses to SARS-CoV-2 essential for vaccine development. However, little information is available defining which determinants of SARS-CoV-2 other than the spike glycoprotein are recognized by the host immune system. In this study, we focus on the SARS-CoV-2 nucleocapsid protein as a suitable candidate target for vaccine formulations. Major B and T cell epitopes of the SARS-CoV-2 N protein are predicted and resulting sequences compared with the homolog immunological domains of other coronaviruses that infect human beings. The most dominant of B cell epitope i s located between 176-206 amino acids in the SRGGSQASSRSSSRSRNSSRNSTPGSSRGTS sequence. Further, we identify sequences which are predicted to bind multiple common MHC I and MHC II alleles. Most notably there is a region of potential T cell cross-reactivity within the SARS-CoV-2 N protein position 102-110 amino acids that traverses multiple human alpha and betacoronaviruses. Vaccination strategies designed to target these conserved epitope regions could generate immune responses that are cross-reactive across human coronaviruses, with potential to protect or modulate disease. Finally, these predictions can facilitate effective vaccine design against this high priority virus. URL: https://www.ncbi.nlm.nih.gov/pubmed/33193414 DOI: 10.3389/fimmu.2020.587615
42. Paltiel AD, Schwartz JL, Zheng A, et al. Clinical Outcomes Of A COVID-19 Vaccine: Implementation Over Efficacy. Health Aff (Millwood). 2020:101377hlthaff202002054. DOI: 10.1377/hlthaff.2020.02054 ABSTRACT: The global effort to develop a coronavirus disease 2019 (COVID-19) vaccine is likely to soon produce one or more authorized vaccines. We examine how different definitions and thresholds of vaccine efficacy, coupled with different levels of implementation effectiveness and background epidemic severity, translate into outcomes including cumulative infections, hospitalizations, and deaths. Using a mathematical simulation of vaccination, we find that factors related to implementation will contribute more to the success of vaccination programs than a vaccine's efficacy as determined in clinical trials. The benefits of a vaccine will decline substantially in the event of manufacturing or deployment delays, significant vaccine hesitancy, or greater epidemic severity. Our findings demonstrate the urgent need for health officials to invest greater financial resources and attention to vaccine production and distribution programs, to redouble efforts to promote public confidence in COVID-19 vaccines, and to encourage continued adherence to other mitigation approaches, even after a vaccine becomes available. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs.]. URL: https://www.ncbi.nlm.nih.gov/pubmed/33211536 DOI: 10.1377/hlthaff.2020.02054
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43. Pandey SC, Pande V, Sati D, et al. Vaccination strategies to combat novel corona virus SARS-CoV-2. Life Sci. 2020;256:117956. DOI: 10.1016/j.lfs.2020.117956 ABSTRACT: The 2019-novel coronavirus disease (COVID-19) is caused by SARS-CoV-2 is transmitted from human to human has recently reported in China. Now COVID-19 has been spread all over the world and declared epidemics by WHO. It has caused a Public Health Emergency of International Concern. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Due to the rapid increase of SARS-CoV-2 infections and unavailability of antiviral therapeutic agents, developing an effective SAR-CoV-2 vaccine is urgently required. SARS-CoV-2 which is genetically similar to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) is an enveloped, single and positive-stranded RNA virus with a genome comprising 29,891 nucleotides, which encode the 12 putative open reading frames responsible for the synthesis of viral structural and nonstructural proteins which are very similar to SARS-CoV and MERS-CoV proteins. In this review we have summarized various vaccine candidates i.e., nucleotide, subunit and vector based as well as attenuated and inactivated forms, which have already been demonstrated their prophylactic efficacy against MERS-CoV and SARS-CoV, so these candidates could be used as a potential tool for the development of a safe and effective vaccine against SARS-CoV-2. URL: https://www.ncbi.nlm.nih.gov/pubmed/32535078 DOI: 10.1016/j.lfs.2020.117956
44. Phillis A. A COVID-19 vaccine-dare to dream. Br J Community Nurs. 2020;25(12):2-7. DOI: 10.12968/bjcn.2020.25.12.598 ABSTRACT: The global desire to produce and deploy a safe and effective vaccine to protect against SARS-CoV-2 infection and the morbidity and mortality subsequent to COVID-19 is unprecedented. The unparalleled speed of research development and access to funding is perhaps equally unique in the history of therapeutic achievement. This article, the third in a series of dedicated to exploring the origins and developments of SARS-CoV-2 within the context of the strategies of infection prevention and control, investigates the theatre behind the extraordinary efforts underpinning the research for therapeutic interventions to halt the COVID-19 pandemic. The Chair of the UK Vaccine Taskforce has stated that the exit strategy depends on a vaccine that is effective in reducing mortality, improving population health by reducing serious disease and protecting the NHS and social care system. This article introduces the major COVID-19 vaccine contenders and considers the challenges and opportunities of an effective global vaccination strategy. URL: https://www.ncbi.nlm.nih.gov/pubmed/33275510 DOI: 10.12968/bjcn.2020.25.12.598
45. Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020. DOI: 10.1056/NEJMoa2034577 ABSTRACT: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. METHODS: In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 mug per dose). BNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. RESULTS: A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. CONCLUSIONS: A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.). URL: https://www.ncbi.nlm.nih.gov/pubmed/33301246 DOI: 10.1056/NEJMoa2034577
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46. Poland GA, Ovsyannikova IG, Crooke SN, et al. SARS-CoV-2 Vaccine Development: Current Status. Mayo Clin Proc. 2020;95(10):2172-88. DOI: 10.1016/j.mayocp.2020.07.021 ABSTRACT: In the midst of the severe acute respiratory syndrome coronavirus 2 pandemic and its attendant morbidity and mortality, safe and efficacious vaccines are needed that induce protective and long-lived immune responses. More than 120 vaccine candidates worldwide are in various preclinical and phase 1 to 3 clinical trials that include inactivated, live- attenuated, viral-vectored replicating and nonreplicating, protein- and peptide-based, and nucleic acid approaches. Vaccines will be necessary both for individual protection and for the safe development of population-level herd immunity. Public-private partnership collaborative efforts, such as the Accelerating COVID-19 Therapeutic Interventions and Vaccines mechanism, are key to rapidly identifying safe and effective vaccine candidates as quickly and efficiently as possible. In this article, we review the major vaccine approaches being taken and issues that must be resolved in the quest for vaccines to prevent coronavirus disease 2019. For this study, we scanned the PubMed database from 1963 to 2020 for all publications using the following search terms in various combinations: SARS, MERS, COVID-19, SARS-CoV-2, vaccine, clinical trial, coronavirus, pandemic, and vaccine development. We also did a Web search for these same terms. In addition, we examined the World Health Organization, Centers for Disease Control and Prevention, and other public health authority websites. We excluded abstracts and all articles that were not written in English. URL: https://www.ncbi.nlm.nih.gov/pubmed/33012348 DOI: 10.1016/j.mayocp.2020.07.021
47. Poonia B, Kottilil S. Immune Correlates of COVID-19 Control. Front Immunol. 2020;11:569611. DOI: 10.3389/fimmu.2020.569611 ABSTRACT: COVID-19 caused by SARS CoV2 emerged in China at the end of 2019 and soon become a pandemic. Since the virus is novel, pre-existing CoV2-specific immunity is not expected to exist in humans, although studies have shown presence of CoV2 cross-reactive T cells in unexposed individuals. Lack of effective immunity in most individuals along with high infectiousness of the virus has resulted in massive global public health emergency. Intense efforts are on to study viral pathogenesis and immune response to help guide prophylactic and therapeutic interventions as well as epidemiological assessments like transmission modeling. To develop an effective vaccine or biologic therapeutic, it is critical to understand the immune correlates of COVID-19 control. At the same time, whether immunity in recovered individuals is effective for preventing re-infection will be important for informing interventions like social distancing. Key questions that are being investigated regarding immune response in COVID-19 which will help these efforts include, investigations of immune response that distinguishes patients with severe versus mild infection or those that recover relative to those that succumb, durability of immunity in recovered patients and relevance of developed immunity in a cured patient for protection against re-infection as well as value of convalescent plasma from recovered patients as a potential therapeutic modality. This is a broad and rapidly evolving area and multiple reports on status of innate and adaptive immunity against SARS-CoV2 are emerging on a daily basis. While many questions remain unanswered for now, the purpose of this focused review is to summarize the current understanding regarding immune correlates of COVID-19 severity and resolution in order to assist researchers in the field to pursue new directions in prevention and control. URL: https://www.ncbi.nlm.nih.gov/pubmed/33133083 DOI: 10.3389/fimmu.2020.569611
48. Pu J, Yu Q, Yin Z, et al. An in-depth investigation of the safety and immunogenicity of an inactivated SARS-CoV-2 vaccine. medRxiv. 2020:2020.09.27.20189548. DOI: 10.1101/2020.09.27.20189548 ABSTRACT: BACKGROUND In-depth investigations of the safety and immunogenicity of inactivated SARS-CoV-2 vaccines are needed.METHOD In a phase I randomized, double-blinded, and placebo-controlled trial involving 192 healthy adults 18-59 years of age, two injections of three different doses (50 EU, 100 EU and 150 EU) of an inactivated SARS-CoV-2 vaccine or the placebo were administered intramuscularly with a 2- or 4-week interval between the injections. The safety and immunogenicity of the vaccine were evaluated within 28 days.FINDING In this study, 191 subjects assigned to three doses groups or the placebo group completed the 28-day trial. There were 44 adverse reactions within the 28 days, most commonly mild pain and redness at the injection site or slight fatigue, and no abnormal variations were observed in 48 cytokines in the serum samples of immunized subjects. The serum samples diluted from 1:32 to 1:4096 and incubated with the virus did not show antibody-dependent enhancement effects (ADEs) with regard to human natural killer cells, macrophages or dendritic cells. At day 14, the seroconversion rates had reached 92%, 100% and 96% with geometric mean titers (GMTs) of 18.0, 54.5 and 37.1, and at day 28, the seroconversion rates had reached 80%, 96% and 92% with GMTs of 10.6, 15.4 and 19.6in 0, 14 and 0, 28 procedures, respectively. Seroconversion was associated with the synchronous
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upregulation of ELISA antibodies against the S protein, N protein and virion and a cytotoxic T lymphocyte (CTL) response. Transcriptome analysis shaped the genetic diversity of immune response induced by the vaccine.INTERPRETATION In a population aged 18-59 years, this inactivated SARS-CoV-2 vaccine was safe and immunogenic.Trial registration NCT04412538FUNDING The National Key R&D Program of China (2020YFC0849700), the Program of Chinese Academy of Medicine Science and the Major Science and Technology Special Projects of Yunnan Province.Competing Interest StatementThe authors have declared no competing interest.Clinical TrialNCT04412538Funding StatementThis work was supported by National Key R&D Program of China (2020YFC0849700), the Program of Chinese Academy of Medicine Science and the Major science and technology special projects of Yunnan Province.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The study protocol was reviewed and approved by the Ethics Committee of the West China Second University Hospital, Sichuan University.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data were available.The raw microarray data were submitted to the National Genomics Data Center (NGDC) and are available (PRJCA003531). URL: https://www.medrxiv.org/content/medrxiv/early/2020/10/06/2020.09.27.20189548.full.pdf DOI: 10.1101/2020.09.27.20189548
49. Romero JR, Bernstein HH. COVID-19 Vaccines: A Primer for Clinicians. Pediatr Ann. 2020;49(12):e532-e6. DOI: 10.3928/19382359-20201116-01 ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the identified cause of coronavirus disease 2019 (COVID-19), continues unabated. This fact, coupled with recurrence of COVID-19 in areas where it had been controlled, highlights the critical need for a safe and effective vaccine to prevent and mitigate this novel virus. The spike protein of SARS-CoV-2 is important in its lifecycle as well as in the development of immunity after human infection. This has prompted the selection of this antigen as a focus in developing COVID-19 vaccines. This article provides (1) a summary of the host immune responses to SARS-CoV-2 infection, (2) the vaccine platforms being used with COVID-19 vaccine candidates undergoing, or about to undergo, Phase III clinical trial testing, and (3) an overview of the key criteria necessary for COVID-19 vaccine efficacy and safety. In addition, the unique concept of vaccine-enhanced disease will be discussed. [Pediatr Ann. 2020;49(12):e532-e536.]. URL: https://www.ncbi.nlm.nih.gov/pubmed/33290571 DOI: 10.3928/19382359-20201116-01
50. Russo G, Pennisi M, Fichera E, et al. In silico trial to test COVID-19 candidate vaccines: a case study with UISS platform. BMC Bioinformatics. 2020;21(Suppl 17):527. DOI: 10.1186/s12859-020-03872-0 ABSTRACT: BACKGROUND: SARS-CoV-2 is a severe respiratory infection that infects humans. Its outburst entitled it as a pandemic emergence. To get a grip on this outbreak, specific preventive and therapeutic interventions are urgently needed. It must be said that, until now, there are no existing vaccines for coronaviruses. To promptly and rapidly respond to pandemic events, the application of in silico trials can be used for designing and testing medicines against SARS-CoV-2 and speed-up the vaccine discovery pipeline, predicting any therapeutic failure and minimizing undesired effects. RESULTS: We present an in silico platform that showed to be in very good agreement with the latest literature in predicting SARS-CoV-2 dynamics and related immune system host response. Moreover, it has been used to predict the outcome of one of the latest suggested approach to design an effective vaccine, based on monoclonal antibody. Universal Immune System Simulator (UISS) in silico platform is potentially ready to be used as an in silico trial platform to predict the outcome of vaccination strategy against SARS-CoV-2. CONCLUSIONS: In silico trials are showing to be powerful weapons in predicting immune responses of potential candidate vaccines. Here, UISS has been extended to be used as an in silico trial platform to speed-up and drive the discovery pipeline of vaccine against SARS-CoV-2. URL: https://www.ncbi.nlm.nih.gov/pubmed/33308153 DOI: 10.1186/s12859-020-03872-0
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51. Sahin U, Muik A, Derhovanessian E, et al. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature. 2020;586(7830):594-9. DOI: 10.1038/s41586-020-2814-7 ABSTRACT: An effective vaccine is needed to halt the spread of the severe acute respiratory syndrome coronavirus-2 (SARS- CoV-2) pandemic. Recently, we reported safety, tolerability and antibody response data from an ongoing placebo- controlled, observer-blinded phase I/II coronavirus disease 2019 (COVID-19) vaccine trial with BNT162b1, a lipid nanoparticle-formulated nucleoside-modified mRNA that encodes the receptor binding domain (RBD) of the SARS-CoV-2 spike protein(1). Here we present antibody and T cell responses after vaccination with BNT162b1 from a second, non- randomized open-label phase I/II trial in healthy adults, 18-55 years of age. Two doses of 1-50 mug of BNT162b1 elicited robust CD4(+) and CD8(+) T cell responses and strong antibody responses, with RBD-binding IgG concentrations clearly above those seen in serum from a cohort of individuals who had recovered from COVID-19. Geometric mean titres of SARS- CoV-2 serum-neutralizing antibodies on day 43 were 0.7-fold (1-mug dose) to 3.5-fold (50-mug dose) those of the recovered individuals. Immune sera broadly neutralized pseudoviruses with diverse SARS-CoV-2 spike variants. Most participants had T helper type 1 (TH1)-skewed T cell immune responses with RBD-specific CD8(+) and CD4(+) T cell expansion. Interferon- gamma was produced by a large fraction of RBD-specific CD8(+) and CD4(+) T cells. The robust RBD-specific antibody, T cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest that it has the potential to protect against COVID-19 through multiple beneficial mechanisms. URL: https://www.ncbi.nlm.nih.gov/pubmed/32998157 DOI: 10.1038/s41586-020-2814-7
52. Salvamani S, Tan HZ, Thang WJ, et al. Understanding the dynamics of COVID-19; implications for therapeutic intervention, vaccine development and movement control. Br J Biomed Sci. 2020;77(4):168-84. DOI: 10.1080/09674845.2020.1826136 ABSTRACT: The COVID-19 disease is caused by the SARS-CoV-2 virus, which is highly infective within the human population. The virus is widely disseminated to almost every continent with over twenty-seven million infections and over ninety- thousand reported deaths attributed to COVID-19 disease. SARS-CoV-2 is a single stranded RNA virus, comprising three main viral proteins; membrane, spike and envelope. The clinical features of COVID-19 disease can be classified according to different degrees of severity, with some patients progressing to acute respiratory distress syndrome, which can be fatal. In addition, many infections are asymptomatic or only cause mild symptoms. As there is no specific treatment for COVID-19 there is considerable endeavour to raise a vaccine against SARS-CoV-2, in addition to engineering neutralizing antibody interventions. In the absence of an effective vaccine, movement controls of varying stringencies have been imposed. Whilst enforced lockdown measures have been effective, they may be less effective against the current strain of SARS-CoV-2, the G614 clade. Conversely, other mutations of the virus, such as the Delta382 variant could reduce the clinical relevance of infection. The front runners in the race to develop an effective vaccine focus on the SARS-Co-V-2 Spike protein. However, vaccines that produce a T-cell response to a wider range of SARS-Co-V-2 viral proteins, may be more effective. Population based studies that determine the level of innate immunity to SARS-CoV-2, from prior exposure to the virus or to other coronaviruses, will have important implications for government imposed movement control and the strategic delivery of vaccination programmes. URL: https://www.ncbi.nlm.nih.gov/pubmed/32942955 DOI: 10.1080/09674845.2020.1826136
53. Sarkar B, Ullah MA, Johora FT, et al. Immunoinformatics-guided designing of epitope-based subunit vaccines against the SARS Coronavirus-2 (SARS-CoV-2). Immunobiology. 2020;225(3):151955. DOI: 10.1016/j.imbio.2020.151955 ABSTRACT: SARS Coronavirus-2 (SARS-CoV-2) pandemic has become a global issue which has raised the concern of scientific community to design and discover a counter-measure against this deadly virus. So far, the pandemic has caused the death of hundreds of thousands of people upon infection and spreading. To date, no effective vaccine is available which can combat the infection caused by this virus. Therefore, this study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics. Upon continual computational experimentation, three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against the SARS-CoV-2. Thereafter, the molecular dynamics simulation and in silico codon adaptation experiments were carried out in order to check biological stability and find effective mass production strategy of the selected vaccine. This study should contribute to uphold the present efforts of the researches to secure a definitive preventative measure against this lethal disease. URL: https://www.ncbi.nlm.nih.gov/pubmed/32517882 DOI: 10.1016/j.imbio.2020.151955
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54. Sharma O, Sultan AA, Ding H, et al. A Review of the Progress and Challenges of Developing a Vaccine for COVID-19. Front Immunol. 2020;11:585354. DOI: 10.3389/fimmu.2020.585354 ABSTRACT: A novel coronavirus, which has been designated as severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), was first detected in December 2019 in Wuhan China and causes the highly infectious disease referred to as COVID- 19. COVID-19 has now spread worldwide to become a global pandemic affecting over 24 million people as of August 26th, 2020 and claimed the life of more than 800,000 people worldwide. COVID-19 is asymptomatic for some individuals and for others it can cause symptoms ranging from flu-like to acute respiratory distress syndrome (ARDS), pneumonia and death. Although it is anticipated that an effective vaccine will be available to protect against COVID-19, at present the world is relying on social distancing and hygiene measures and repurposed drugs. There is a worldwide effort to develop an effective vaccine against SARS-CoV-2 and, as of late August 2020, there are 30 vaccines in clinical trials with over 200 in various stages of development. This review will focus on the eight vaccine candidates that entered Phase 1 clinical trials in mid-May, including AstraZeneca/Oxford's AZD1222, Moderna's mRNA-1273 and Sinovac's CoronaVac vaccines, which are currently in advanced stages of vaccine development. In addition to reviewing the different stages of vaccine development, vaccine platforms and vaccine candidates, this review also discusses the biological and immunological basis required of a SARS-CoV-2 vaccine, the importance of a collaborative international effort, the ethical implications of vaccine development, the efficacy needed for an immunogenic vaccine, vaccine coverage, the potential limitations and challenges of vaccine development. Although the demand for a vaccine far surpasses the production capacity, it will be beneficial to have a limited number of vaccines available for the more vulnerable population by the end of 2020 and for the rest of the global population by the end of 2021. URL: https://www.ncbi.nlm.nih.gov/pubmed/33163000 DOI: 10.3389/fimmu.2020.585354
55. Shih HI, Wu CJ, Tu YF, et al. Fighting COVID-19: A quick review of diagnoses, therapies, and vaccines. Biomed J. 2020;43(4):341-54. DOI: 10.1016/j.bj.2020.05.021 ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic caused by a novel coronavirus, SARS-CoV-2, has infected more than 22 million individuals and resulted in over 780,000 deaths globally. The rapid spread of the virus and the precipitously increasing numbers of cases necessitate the urgent development of accurate diagnostic methods, effective treatments, and vaccines. Here, we review the progress of developing diagnostic methods, therapies, and vaccines for SARS-CoV-2 with a focus on current clinical trials and their challenges. For diagnosis, nucleic acid amplification tests remain the mainstay diagnostics for laboratory confirmation of SARS-CoV-2 infection, while serological antibody tests are used to aid contact tracing, epidemiological, and vaccine evaluation studies. Viral isolation is not recommended for routine diagnostic procedures due to safety concerns. Currently, no single effective drug or specific vaccine is available against SARS-CoV-2. Some candidate drugs targeting different levels and stages of human responses against COVID-19 such as cell membrane fusion, RNA-dependent RNA polymerase, viral protease inhibitor, interleukin 6 blocker, and convalescent plasma may improve the clinical outcomes of critical COVID-19 patients. Other supportive care measures for critical patients are still necessary. Advances in genetic sequencing and other technological developments have sped up the establishment of a variety of vaccine platforms. Accordingly, numerous vaccines are under development. Vaccine candidates against SARS-CoV-2 are mainly based upon the viral spike protein due to its vital role in viral infectivity, and most of these candidates have recently moved into clinical trials. Before the efficacy of such vaccines in humans is demonstrated, strong international coordination and collaboration among studies, pharmaceutical companies, regulators, and governments are needed to limit further damage due the emerging SARS-CoV-2 virus. URL: https://www.ncbi.nlm.nih.gov/pubmed/32532623 DOI: 10.1016/j.bj.2020.05.021
56. Singh DD, Han I, Choi EH, et al. Immunopathology, host-virus genome interactions, and effective vaccine development in SARS-CoV-2. Comput Struct Biotechnol J. 2020;18:3774-87. DOI: 10.1016/j.csbj.2020.11.011 ABSTRACT: Coronaviruses are a group of enveloped RNA viruses that are diversely found in humans and now declared a global pandemic by the World Health Organization in March 2020. The population's susceptibility to these highly pathogenic coronaviruses has contributed to large outbreaks, evolved into public health events, and rapidly transmitted globally. Thus, there is an urgent need to develop effective therapies and vaccines against this disease. In the primary stage of severe acute respiratory syndrome coronavirus (SARS-COV-2) infection, the signs and symptoms are nonspecific, and many more cases have been observed than initially expected. Genome sequencing is performed regularly to identify genetic changes to SARS-COV-2, and vaccine development is focused on manufacture, production, and based on specific problems,
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and very few are available on recent developments in the prevention of outbreaks. The aim of this review article to explore recent updates on SARS-COV-2 in the context of pathogenesis during disease progression, and innate acquired mechanisms of defense, This includes advances in diagnostics, susceptibility, and severity of host-virus genome interactions, modes of transmission, active compounds being used in pre-clinical and clinical trials for the treatment of patients, vaccine developments, and the effectiveness of SARS-COV-2 prevention and control measures. We have summarized the importance of pathophysiology immune response, Diagnostics, vaccine development currently approaches explored for SARS-COV-2. URL: https://www.ncbi.nlm.nih.gov/pubmed/33235690 DOI: 10.1016/j.csbj.2020.11.011
57. Tahir Ul Qamar M, Shahid F, Aslam S, et al. Reverse vaccinology assisted designing of multiepitope-based subunit vaccine against SARS-CoV-2. Infect Dis Poverty. 2020;9(1):132. DOI: 10.1186/s40249-020-00752-w ABSTRACT: BACKGROUND: Coronavirus disease 2019 (COVID-19) linked with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause severe illness and life-threatening pneumonia in humans. The current COVID-19 pandemic demands an effective vaccine to acquire protection against the infection. Therefore, the present study was aimed to design a multiepitope-based subunit vaccine (MESV) against COVID-19. METHODS: Structural proteins (Surface glycoprotein, Envelope protein, and Membrane glycoprotein) of SARS-CoV-2 are responsible for its prime functions. Sequences of proteins were downloaded from GenBank and several immunoinformatics coupled with computational approaches were employed to forecast B- and T- cell epitopes from the SARS-CoV-2 highly antigenic structural proteins to design an effective MESV. RESULTS: Predicted epitopes suggested high antigenicity, conserveness, substantial interactions with the human leukocyte antigen (HLA) binding alleles, and collective global population coverage of 88.40%. Taken together, 276 amino acids long MESV was designed by connecting 3 cytotoxic T lymphocytes (CTL), 6 helper T lymphocyte (HTL) and 4 B-cell epitopes with suitable adjuvant and linkers. The MESV construct was non-allergenic, stable, and highly antigenic. Molecular docking showed a stable and high binding affinity of MESV with human pathogenic toll-like receptors-3 (TLR3). Furthermore, in silico immune simulation revealed significant immunogenic response of MESV. Finally, MEV codons were optimized for its in silico cloning into the Escherichia coli K-12 system, to ensure its increased expression. CONCLUSION: The MESV developed in this study is capable of generating immune response against COVID-19. Therefore, if designed MESV further investigated experimentally, it would be an effective vaccine candidate against SARS-CoV-2 to control and prevent COVID-19. URL: https://www.ncbi.nlm.nih.gov/pubmed/32938504 DOI: 10.1186/s40249-020-00752-w
58. Voysey M, Clemens SAC, Madhi SA, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. The Lancet. 2020. DOI: 10.1016/s0140-6736(20)32661-1 DOI: 10.1016/s0140-6736(20)32661-1
59. Walsh EE, Frenck RW, Jr., Falsey AR, et al. Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates. N Engl J Med. 2020;383(25):2439-50. DOI: 10.1056/NEJMoa2027906 ABSTRACT: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (Covid-19), have spread to millions of persons worldwide. Multiple vaccine candidates are under development, but no vaccine is currently available. Interim safety and immunogenicity data about the vaccine candidate BNT162b1 in younger adults have been reported previously from trials in Germany and the United States. METHODS: In an ongoing, placebo-controlled, observer-blinded, dose-escalation, phase 1 trial conducted in the United States, we randomly assigned healthy adults 18 to 55 years of age and those 65 to 85 years of age to receive either placebo or one of two lipid nanoparticle-formulated, nucleoside-modified RNA vaccine candidates: BNT162b1, which encodes a secreted trimerized SARS-CoV-2 receptor-binding domain; or BNT162b2, which encodes a membrane-anchored SARS-CoV-2 full-length spike, stabilized in the prefusion conformation. The primary outcome was safety (e.g., local and systemic reactions and adverse events); immunogenicity was a secondary outcome. Trial groups were defined according to vaccine candidate, age of the participants, and vaccine dose level (10 mug, 20 mug, 30 mug, and 100 mug). In all groups but one, participants received two doses, with a 21-day interval between doses; in one group (100 mug of BNT162b1), participants received one dose. RESULTS: A total of 195 participants underwent randomization. In each of 13 groups of 15 participants, 12 participants received vaccine and 3 received placebo. BNT162b2 was associated with a lower incidence and severity of systemic reactions than BNT162b1, particularly in older adults. In both younger and older adults, the two vaccine
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candidates elicited similar dose-dependent SARS-CoV-2-neutralizing geometric mean titers, which were similar to or higher than the geometric mean titer of a panel of SARS-CoV-2 convalescent serum samples. CONCLUSIONS: The safety and immunogenicity data from this U.S. phase 1 trial of two vaccine candidates in younger and older adults, added to earlier interim safety and immunogenicity data regarding BNT162b1 in younger adults from trials in Germany and the United States, support the selection of BNT162b2 for advancement to a pivotal phase 2-3 safety and efficacy evaluation. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.). URL: https://www.ncbi.nlm.nih.gov/pubmed/33053279 DOI: 10.1056/NEJMoa2027906
60. Wang J, Peng Y, Xu H, et al. The COVID-19 Vaccine Race: Challenges and Opportunities in Vaccine Formulation. AAPS PharmSciTech. 2020;21(6):225. DOI: 10.1208/s12249-020-01744-7 ABSTRACT: In the race for a safe and effective vaccine against coronavirus disease (COVID)-19, pharmaceutical formulation science plays a critical role throughout the development, manufacturing, distribution, and vaccination phases. The proper choice of the type of vaccine, carrier or vector, adjuvant, excipients, dosage form, and route of administration can directly impact not only the immune responses induced and the resultant efficacy against COVID-19, but also the logistics of manufacturing, storing and distributing the vaccine, and mass vaccination. In this review, we described the COVID-19 vaccines that are currently tested in clinical trials and provided in-depth insight into the various types of vaccines, their compositions, advantages, and potential limitations. We also addressed how challenges in vaccine distribution and administration may be alleviated by applying vaccine-stabilization strategies and the use of specific mucosal immune response-inducing, non-invasive routes of administration, which must be considered early in the development process. URL: https://www.ncbi.nlm.nih.gov/pubmed/32761294 DOI: 10.1208/s12249-020-01744-7
61. Wu S, Zhong G, Zhang J, et al. A single dose of an adenovirus-vectored vaccine provides protection against SARS-CoV- 2 challenge. Nat Commun. 2020;11(1):4081. DOI: 10.1038/s41467-020-17972-1 ABSTRACT: The unprecedented coronavirus disease 2019 (COVID-19) epidemic has created a worldwide public health emergency, and there is an urgent need to develop an effective vaccine to control this severe infectious disease. Here, we find that a single vaccination with a replication-defective human type 5 adenovirus encoding the SARS-CoV-2 spike protein (Ad5-nCoV) protect mice completely against mouse-adapted SARS-CoV-2 infection in the upper and lower respiratory tracts. Additionally, a single vaccination with Ad5-nCoV protects ferrets from wild-type SARS-CoV-2 infection in the upper respiratory tract. This study suggests that the mucosal vaccination may provide a desirable protective efficacy and this delivery mode is worth further investigation in human clinical trials. URL: https://www.ncbi.nlm.nih.gov/pubmed/32796842 DOI: 10.1038/s41467-020-17972-1
62. Yellapu NK, Patel S, Zhang B, et al. Evolutionary Analysis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS- CoV-2) Reveals Genomic Divergence with Implications for Universal Vaccine Efficacy. Vaccines (Basel). 2020;8(4):1-15. DOI: 10.3390/vaccines8040591 ABSTRACT: Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is one of the pressing contemporary public health challenges. Investigations into the genomic structure of SARS-CoV-2 may inform ongoing vaccine development efforts and/or provide insights into vaccine efficacy to fight against COVID-19. Evolutionary analysis of 540 genomes spanning 20 different countries/territories was conducted and revealed an increase in the genomic divergence across successive generations. The ancestor of the phylogeny was found to be the isolate from the 2019/2020 Wuhan outbreak. Its transmission was outlined across 20 countries/territories as per genomic similarity. Our results demonstrate faster evolving variations in the genomic structure of SARS-CoV-2 when compared to the isolates from early stages of the pandemic. Genomic alterations were predominantly located and mapped onto the reported vaccine candidates of structural genes, which are the main targets for vaccine candidates. S protein showed 34, N protein 25, E protein 2, and M protein 3 amino acid variations in 246 genomes among 540. Among identified mutations, 23 in S protein, 1 in E, 2 from M, and 7 from N protein were mapped with the reported vaccine candidates explaining the possible implications on universal vaccines. Hence, potential target regions for vaccines would be ideally chosen from the structural regions of the genome that lack high variation. The increasing variations in the genome of SARS-CoV-2 together with our observations in structural genes have important implications for the efficacy of a successful universal vaccine against SARS- CoV-2. URL: https://www.ncbi.nlm.nih.gov/pubmed/33050053
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DOI: 10.3390/vaccines8040591
63. Zeng C, Hou X, Yan J, et al. Leveraging mRNA Sequences and Nanoparticles to Deliver SARS-CoV-2 Antigens In Vivo. Adv Mater. 2020;32(40):e2004452. DOI: 10.1002/adma.202004452 ABSTRACT: SARS-CoV-2 has become a pandemic worldwide; therefore, an effective vaccine is urgently needed. Recently, messenger RNAs (mRNAs) have emerged as a promising platform for vaccination. In this work, the untranslated regions (UTRs) of mRNAs are systematically engineered in order to enhance protein production. Through a comprehensive analysis of endogenous gene expression and de novo design of UTRs, the optimal combination of 5' and 3' UTR are identified and termed NASAR, which are 5- to 10-fold more efficient than the tested endogenous UTRs. More importantly, NASAR mRNAs delivered by lipid-derived TT3 nanoparticles trigger a dramatic expression of potential SARS-CoV-2 antigens. The antigen- specific antibodies induced by TT3-nanoparticles and NASAR mRNAs are over two orders of magnitude more than that induced by the FDA-approved lipid nanoparticle material MC3 in vaccinated mice. These NASAR mRNAs merit further development as alternative SARS-CoV-2 vaccines. URL: https://www.ncbi.nlm.nih.gov/pubmed/32875709 DOI: 10.1002/adma.202004452
64. Zhu F-C, Guan X-H, Li Y-H, et al. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet. 2020;396(10249):479-88. DOI: 10.1016/s0140-6736(20)31605-6 DOI: 10.1016/s0140-6736(20)31605-6
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