DOCSLIB.ORG

Gene-Based Vaccines (GBV)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Gene-Based Vaccines (GBV) Advanced Drug Delivery Reviews 170 (2021) 113–141 Contents lists available at ScienceDirect Advanced Drug Delivery Reviews journal homepage: www.elsevier.com/locate/addr Advances in gene-based vaccine platforms to address the COVID-19 pandemic Deborah Pushparajah a,1, Salma Jimenez a,c,1,ShirleyWonga,HibahAlattasa, Nafiseh Nafissi b, Roderick A. Slavcev a,b,c,⁎ a School of Pharmacy, University of Waterloo, 10A Victoria St S, Kitchener N2G 1C5, Canada b Mediphage Bioceuticals, 661 University Avenue, Suite 1300, Toronto, ON, M5G 0B7, Canada c Theraphage, 151 Charles St W Suite # 199, Kitchener, ON, N2G 1H6, Canada article info abstract Article history: The novel betacoronavirus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has spread across Received 1 October 2020 the globe at an unprecedented rate since its first emergence in Wuhan City, China in December 2019. Scientific Received in revised form 23 December 2020 communities around the world have been rigorously working to develop a potent vaccine to combat COVID-19 Accepted 1 January 2021 (coronavirus disease 2019), employing conventional and novel vaccine strategies. Gene-based vaccine platforms Available online 7 January 2021 based on viral vectors, DNA, and RNA, have shown promising results encompassing both humoral and cell-mediated immune responses in previous studies, supporting their implementation for COVID-19 vaccine de- Keywords: Coronavirus velopment. In fact, the U.S. Food and Drug Administration (FDA) recently authorized the emergency use of two COVID-19 RNA-based COVID-19 vaccines. We review current gene-based vaccine candidates proceeding through clinical SARS-CoV-2 trials, including their antigenic targets, delivery vehicles, and route of administration. Important features of pre- Vaccines vious gene-based vaccine developments against other infectious diseases are discussed in guiding the design and DNA vaccines development of effective vaccines against COVID-19 and future derivatives. RNA vaccines ©2021ElsevierB.V.Allrightsreserved. Replicative viral vaccines Non-replicative viral vaccines Contents 1. Introduction............................................................... 114 2. COVID-19vaccinetargets......................................................... 115 2.1. Optimalantigenselection..................................................... 115 2.2. COVID-19immunogenictargets.................................................. 115 2.3. AminoacidsequencealignmentofstructuralproteinsfromCoronavirus................................ 116 3. Novelgene-basedvaccineplatforms.................................................... 116 3.1. Viralvectorvaccines........................................................ 116 3.2. Nucleicacidvaccines....................................................... 117 4. Gene-basedvaccineadministration.................................................... 118 4.1. Routeofadministration...................................................... 118 4.1.1. Mucosalvaccination.................................................... 118 4.1.2. Parenteralvaccination................................................... 118 Abbreviations: a.a, amino acid; AAV, adeno-associated virus; ACE2, angiotensin converting enzyme 2; ADE, antibody dependent enhancement; BGH, bovine growth hormone; ChAd, chimpanzee adenovirus; COVID-19, coronavirus disease 2019; CMV, cytomegalovirus; DPP4, dipeptidyl peptidase 4; E, envelope; EP, electroporation; GBV, gene-based vaccine; GP, gly- coprotein; GC, guanine-cytosine; HA, hemagglutinin; HAI, hemagglutinin inhibition; IFN, interferon; IIV, inactivated influenza virus vaccine; IL, interleukin; LNP, lipid nanoparticle; Lunar, lipid-enabled and unlocked nucleomonomer agent modified RNA; M, membrane; MIV, monovalent inactivated virus; MERS-CoV, Middle East respiratory syndrome coronavirus; MV, mea- sles virus; MVA, modified vaccinia virus Ankara; N, nucleocapsid; OGN, oligodeoxynucleotide; ORF, open reading frame; polyA, polyadenylation; RSV, respiratory syncytial virus; saRNA, self-amplifying RNA; SARS-CoV, severe acute respiratory syndrome coronavirus; SARS-CoV-2, severe acute respiratory syndrome 2; SLE, systemic lupus erythematosus; S, spike; RBD, re- ceptor binding domain; Th, T helper; TLR, toll-like receptor; TNF, tumor necrosis factor; tPA, tissue plasminogen activator; VSV, vesicular stomatitis virus; WNV, West Nile virus. ⁎ Corresponding author at: School of Pharmacy, University of Waterloo, 10A Victoria St S, Kitchener ON, N2G 1C5, Canada. E-mail address: [email protected] (R.A. Slavcev). 1 Deborah Pushparajah and Salma Jimenez equally contributed to this work. https://doi.org/10.1016/j.addr.2021.01.003 0169-409X/© 2021 Elsevier B.V. All rights reserved. D. Pushparajah, S. Jimenez, S. Wong et al. Advanced Drug Delivery Reviews 170 (2021) 113–141 4.2. Noveldeliverytools........................................................ 119 5. Immunityandsafetyofpreviousgene-basedvaccines............................................ 119 5.1. Previousviralvectorvaccineimmunityandsafety.......................................... 119 5.1.1. Non-replicativeviralvectorvaccines............................................ 119 5.1.2. Replicativeviralvectorvaccines.............................................. 122 5.2. PreviousDNAvaccineimmunityandsafety............................................. 123 5.3. PreviousRNAvaccineimmunityandsafety............................................. 123 6. COVID-19gene-basedvaccines...................................................... 124 6.1. Viralvectorvaccines........................................................ 124 6.2. DNAvaccines........................................................... 126 6.3. RNAvaccines........................................................... 126 7. Adjuvantadministration......................................................... 130 8. Immuneenhancementofgene-basedvaccines............................................... 132 8.1. Antibodydependentenhancement................................................. 132 8.2. Th2immunopathology....................................................... 132 9. Conclusions............................................................... 133 Acknowledgements.............................................................. 133 References.................................................................. 133 1. Introduction infection rates, longer incubation periods, and increased levels of asymptomatic transmission [5]. The 2019 novel coronavirus outbreak (COVID-19), caused by the As of December 2020, WHO reports 215 COVID-19 vaccine candi- severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) corona- dates in development [6]. Of these, 52 are undergoing clinical evaluation virus, was declared a global pandemic on March 11, 2020 by the World and 163 are still in preclinical development. These candidates encom- Health Organization (WHO) and has since imparted significant morbid- pass a diverse selection of vaccine platforms: protein-based (subunit ity and fatalities as governing bodies scramble to mitigate looming eco- and virus-like particle), virus-based (live attenuated and inactivated), nomic fallout. As of December 2020, this highly transmissible virus has and novel gene delivery strategies such as nucleic acid (DNA and already infected over 65 million worldwide, resulting in more than 1.5 RNA), and viral vector (replicative and non-replicative) (Fig. 1). Con- million deaths [1]. Born out of mutation, SARS-CoV-2 will continue to ventional strategies, such as inactivated viral, live attenuated viral, and drift as a response to evolutionary pressures, and as the outbreak con- protein subunit vaccines have demonstrated successful outcomes in tinues, it will spread and kill indiscriminately. The need for protective the past, but tend to confer complications with safety, limited cross- solutions and, in particular, a safe and effective vaccine is of highest pri- protection and immunogenicity [7]. Novel vaccine platforms include ority and paramount urgency. virus-like particles, viral vectors, and nucleic acid vaccines [8]. Gene- As a member of the Coronavirdae family, SARS-CoV-2 is classified as a based vaccines (GBVs), including both viral vectors and nucleic acid vac- betacoronavirus which is characterized by having a single-stranded, cines, genetically encode an antigen to be delivered. They depend on the positive-sense, enveloped RNA genome varying from 26.5 to 31.7 kb successful expression of delivered gene cassettes to peptide antigen(s), in size [2]. The virus is one of six human transmissible coronaviruses dis- which must then be presented to immune cells to stimulate an immune covered to date [3]. COVID-19 presents similar features and symptoms response. Viral vector vaccines have previously been approved by to previous outbreaks of related betacoronaviruses: severe acute respi- health authorities [9]. The first two RNA-based vaccines against ratory syndrome coronavirus (SARS-CoV) and Middle East respiratory COVID-19 were recently approved by the U.S. FDA for emergency use syndrome coronavirus (MERS-CoV), which emerged in 2002 and [10,11,12]. This renders DNA-based vaccines as the only completely un- 2012, respectively [4,5]. Although these viruses share considerable tested therapeutic vaccine approach for human application [13]. sequence similarity, SARS-CoV-2 has thus far demonstrated higher Heightened interest in the development of GBVs is attributed to some protein subunit (71) gene-based (98) non-replicating viral
Load more

Recommended publications
  • Ifs Recommendations for Covid 19 Vaccination Before Art
    16 – 17 JULY 2020 PRAGATI MAIDAN - DELHI INDIAN FERTILITY SOCIETY IFS RECOMMENDATIONS FOR COVID 19 VACCINATION BEFORE ART IFS SECRETARIAT +91 11 40018184 +91 9899308083 indianferlitysociety [email protected] www.indianferlitysociety.org indianferlitysociety 302, 3rd Floor, Kailash Building, ifsdelhi 26, Kasturba Gandhi Marg, C.P. New Delhi - 110001 Cosmo Tech is the Most Important Trade show for the Suppliers to EXPAND Strengthen Increase Multiply Profits New Markets Pan New Market Customer Base India & World Customer Soaring Boost Network Brand Sales Brand Recall Value with the Industry Visibility ORGANIZED BY CALL EMAIL +91 9971811937 [email protected] +91 9999302797 [email protected] +91 9811141938 [email protected] W W W .C O SMO TEC HEXPO IND IA .C O M Dr. Sudha Prasad Dr. Neena Malhotra President Secretary General Indian Fertility Society Indian Fertility Society Director, Matritava Advanced IVF & Professor, ART Centre, Department of Training Cenre, Vasant Vihar, New Delhi Obstetrics and Gynaecology, AIIMS, New Delhi Dr. Sonia Malik Dr. Kuldeep Jain Past President Indian Fertility Society, Past President Indian Fertility Society, Director & Nova Southend Fertility & Director, KJIVF New Delhi IVF Delhi NCR Dr. KU Kunjumoideen Dr. A K Pandey Joint Secretary Indian Fertility Society, Dean Academics &. Co Ordinator Director ARMC IVF Calicut. Molecular Lab. ESI Medical college Faridabad Dr. Charu Jandial Dr. Sumita Aggarwal Member IFS, Consultant, Member IFS, Fellow, Nova Southend Fertility & IVF Delhi NCR Nova Southend Fertility & IVF Delhi NCR Introduction The coronavirus pandemic has wreaked havoc on life In these trying mes, as sociees are gradually trying to and healthcare globally. According to WHO database as return to a state of normalcy, it is also important to on 7th June 2021, there have been 173 million consider sexual and reproducve health of people.
    [Show full text]
  • Review of COVID-19 Vaccine Subtypes, Efficacy and Geographical Distributions Andre Ian Francis ‍ ‍ ,1 Saudah Ghany,1 Tia Gilkes,1 Srikanth Umakanthan2
    Review Postgrad Med J: first published as 10.1136/postgradmedj-2021-140654 on 6 August 2021. Downloaded from Review of COVID-19 vaccine subtypes, efficacy and geographical distributions Andre Ian Francis ,1 Saudah Ghany,1 Tia Gilkes,1 Srikanth Umakanthan2 1Department of Clinical Medical ABSTRACT 2021, the Ad26.COV2.S, developed by Janssen Sciences, The Faculty of Medical As of 1 May 2021, there have been 152 661 445 (Johnson & Johnson) and Moderna on 30 April.4 Sciences, The University of the COVAX, coordinated by WHO, Gavi: The West Indies, St. Augustine, Covid-19 cases with 3 202 256 deaths globally. Trinidad and Tobago This pandemic led to the race to discover a vaccine Vaccine Alliance, the Coalition for Epidemic 2Pathology unit, Department to achieve herd immunity and curtail the damaging Preparedness Innovations (CEPI), acts as a of Paraclinical Sciences, The effects of Covid-19. This study aims to discuss the most programme that supports the development of University Of The West Indies, St. COVID-19 vaccine candidates and negotiates their Augustine, Trinidad and Tobago recent WHO-approved Covid-19 vaccine subtypes, their status and geographical scheduled updates as of 4 pricing to ensure low- and- middle- income countries have a fair shot at receiving vaccines.5 Correspondence to May 2021. The keywords “Covid-19, Vaccines, Pfizer, Mr. Andre Ian Francis, The BNT162b2, AstraZeneca, AZD1222, Moderna, mRNA- This article aims at discussing the most recent University of the West Indies, St. 1273, Janssen, Ad26.COV2.S” were typed into PubMed. WHO- approved COVID-19 vaccine subtypes, their Augustine, Trinidad and Tobago; Thirty Two relevant PubMed articles were included in status and geographical scheduled updates as of 4 andre.
    [Show full text]
  • Considerations for Causality Assessment of Neurological And
    Occasional essay J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2021-326924 on 6 August 2021. Downloaded from Considerations for causality assessment of neurological and neuropsychiatric complications of SARS- CoV-2 vaccines: from cerebral venous sinus thrombosis to functional neurological disorder Matt Butler ,1 Arina Tamborska,2,3 Greta K Wood,2,3 Mark Ellul,4 Rhys H Thomas,5,6 Ian Galea ,7 Sarah Pett,8 Bhagteshwar Singh,3 Tom Solomon,4 Thomas Arthur Pollak,9 Benedict D Michael,2,3 Timothy R Nicholson10 For numbered affiliations see INTRODUCTION More severe potential adverse effects in the open- end of article. The scientific community rapidly responded to label phase of vaccine roll- outs are being collected the COVID-19 pandemic by developing novel through national surveillance systems. In the USA, Correspondence to SARS- CoV-2 vaccines (table 1). As of early June Dr Timothy R Nicholson, King’s roughly 372 adverse events have been reported per College London, London WC2R 2021, an estimated 2 billion doses have been million doses, which is a lower rate than expected 1 2LS, UK; timothy. nicholson@ administered worldwide. Neurological adverse based on the clinical trials.6 kcl. ac. uk events following immunisation (AEFI), such as In the UK, adverse events are reported via the cerebral venous sinus thrombosis and demyelin- MB and AT are joint first Coronavirus Yellow Card reporting website. As of ating episodes, have been reported. In some coun- authors. early June 2021, approximately 250 000 Yellow tries, these have led to the temporary halting of BDM and TRN are joint senior Cards have been submitted, equating to around authors.
    [Show full text]
  • Different Types of COVID-19 Vaccines
    Pfizer-BioNTech Help stop the pandemic Type of vaccine: Messenger RNA, or mRNA, a genetic Different Types material that tells your body how to make proteins that by getting vaccinated triggers an immune response inside our bodies of COVID-19 Effectiveness: 95% based on clinical trials Even if you are undocumented Common side effects: Pain and/or swelling in the arm and/or don’t have insurance, you and tiredness, headache, muscle pain, chills, fever, or can get the vaccine—for free. Vaccines: nausea in the body that may last two days Recommended Ages: 16 and older (currently testing the vaccine in kids ages 12-15) Understanding How Dosage: Two shots, 21 days apart They Work Visit VaccinateALL58.com Moderna for the newest information about when and where the vaccine Type of vaccine: Messenger RNA, or mRNA, a genetic will be available to you. material that tells your body how to make proteins that triggers an immune response inside our bodies Sign up at myturn.ca.gov or Effectiveness: 94.1% based on clinical trials call 1-833-422-4255 to find out Common side effects: Pain and/or swelling in the arm if it’s your turn to get vaccinated and and tiredness, headache, muscle pain, chills, fever, or schedule vaccination appointments. nausea in the body that may last two days Recommended Ages: 18 years and older (currently testing the vaccine in kids ages 12-17) Dosage: Two shots, 28 days apart Johnson & Johnson Follow us on social media for more COVID-19 tips and information. Type of vaccine: A viral vector, it uses a harmless version of a different
    [Show full text]
  • Adenoviral Vector COVID-19 Vaccines: Process and Cost Analysis
    processes Article Adenoviral Vector COVID-19 Vaccines: Process and Cost Analysis Rafael G. Ferreira 1,* , Neal F. Gordon 2, Rick Stock 2 and Demetri Petrides 3 1 Intelligen Brasil, Sao Paulo 01227-200, Brazil 2 BDO USA, LLP, Boston, MA 02110, USA; [email protected] (N.F.G.); [email protected] (R.S.) 3 Intelligen, Inc., Scotch Plains, NJ 07076, USA; [email protected] * Correspondence: [email protected] Abstract: The COVID-19 pandemic has motivated the rapid development of numerous vaccines that have proven effective against SARS-CoV-2. Several of these successful vaccines are based on the adenoviral vector platform. The mass manufacturing of these vaccines poses great challenges, especially in the context of a pandemic where extremely large quantities must be produced quickly at an affordable cost. In this work, two baseline processes for the production of a COVID-19 adenoviral vector vaccine, B1 and P1, were designed, simulated and economically evaluated with the aid of the software SuperPro Designer. B1 used a batch cell culture viral production step, with a viral titer of 5 × 1010 viral particles (VP)/mL in both stainless-steel and disposable equipment. P1 used a perfusion cell culture viral production step, with a viral titer of 1 × 1012 VP/mL in exclusively disposable equipment. Both processes were sized to produce 400 M/yr vaccine doses. P1 led to a smaller cost per dose than B1 ($0.15 vs. $0.23) and required a much smaller capital investment ($126 M vs. $299 M). The media and facility-dependent expenses were found to be the main contributors to the operating cost.
    [Show full text]
  • An Overview of COVID Vaccine Clinical Trial Results & Some Challenges
    An overview of COVID vaccine clinical trial results & some challenges DCVMN Webinar December 8th, 2020 Access to COVID-19 tools ACCESSACCESS TO TOCOVID-19 COVID-19 TOOLS TOOLS (ACT) (ACT) ACCELERATOR ACCELERATOR (ACT) accelerator A GlobalA GlobalCollaboration Collaboration to Accelerate tothe AccelerateDevelopment, the Production Development, and Equitable Production Access to New and Equitable AccessCOVID-19 to New diagnostics, COVID-19 therapeutics diagnostics, and vaccines therapeutics and vaccines VACCINES DIAGNOSTICS THERAPEUTICS (COVAX) Development & Manufacturing Led by CEPI, with industry Procurement and delivery at scale Led by Gavi Policy and allocation Led by WHO Key players SOURCE: (ACT) ACCELERATOR Commitment and Call to Action 24th April 2020 ACT-A / COVAX governance COVAX COORDINATION MEETING CEPI Board Co-Chair: Jane Halton Co-Chair: Dr. Ngozi Gavi Board Workstream leads + DCVMN and IFPMA-selected Reps As needed – R&D&M Chair; COVAX IPG Chair Development & Manufacturing Procurement and delivery Policy and allocation (COVAX) at scale Led by (with industry) Led by Led by R&D&M Investment Committee COVAX Independent Product Group Technical Review Group Portfolio Group Vaccine Teams SWAT teams RAG 3 COVAX SWAT teams are being set up as a joint platform to accelerate COVID- 19 Vaccine development and manufacturing by addressing common challenges together Timely and targeted Multilateral Knowledge-based Resource-efficient Addresses specific cross- Establishes a dialogue Identifies and collates Coordinates between developer technical and global joint effort most relevant materials different organizations/ challenges as they are across different COVID-19 and insights across the initiatives to limit raised and/or identified vaccines organizations broader COVID-19 duplications and ensure on an ongoing basis (incl.
    [Show full text]
  • Update 50 (15Th of December 2020)
    Update 50 (15th of December 2020) Information about Infection disease COVID-19 (novel coronavirus) Force Health Protection Branch FHPB (former DHSC) NATO MILMED COE in Munich 15th of December 2020 email: [email protected] In December 2019, a novel coronavirus emerged in Wuhan City, China. Since then the virus spread to 65 countries including Europe and America. Since then the virus showed evidence for human-to-human transmission as well as evidence of asymptomatic transmission. At 30th January 2020 WHO declared a Public Health Emergency of International Concern. The disease was formally named COVID-19 on 11th of February. The virus itself has been named SARS-CoV-2. On 11th of March 2020 WHO characterized the disease as a pandemic. HIGHLIGHTS/NEWS GLOBALLY ↗ • GBR/WHO: A new variant of the virus could be responsible for the renewed high number of cases in the UK, among other things, which 72 879 777 confirmed cases could be "in connection with the faster spread in the south of England". 47 710 950 recovered So far, 1000 cases have been identified. 1 622 200 deaths The WHO emphasized that the new variant would now be examined. EU/EEA and the UK ↘ However, there is no evidence that the strain behaves differently than 21 936 276 existing virus types. "We saw many variants, this virus evolves and confirmed cases changes over time." 10 689 950 recovered • Sputnik V: The developers of the Russian coronavirus vaccine Sputnik 479 566 deaths V explain that it creates 91.4 percent protection against the lung disease USA ↗ Covid-19.
    [Show full text]
  • A Best Shot at Global Public Health Response
    FOCAL POINT ON VACCINE RESEARCH IN ASIA ADVERTISEMENT FEATURE A best shot at global public health response From tuberculosis and pneumonia, to Ebola and Zika, a Chinese biotech firm is DEVELOPING HIGH-QUALITY VACCINES to address global health challenges. In 2017, China’s food and drug resource-limited tropical areas. authority approved its first Such ease of storage and Ebola virus vaccine, making handling gives the Ad5-EBOV China only the second country to vaccine an edge over competing licence a vaccine for this deadly products from multinational disease. Causing a sudden pharmaceutical companies. onset of high fever, followed by With recent reports of new vomiting, diarrhoea, and internal Ebola outbreaks in Democratic and external bleeding, Ebola, Republic of the Congo, the Ad5- with mortality rates varying EBOV vaccine, already approved Chinese returnees, who held based pneumococcal vaccine currently available in China. vaccine products in the pipeline, conjugate vaccines. With various The company is also from 40% to 90%, has no in China for emergency use, senior management and (PBPV), represent innovative The company developed covering 12 disease areas. carrier proteins, including the equipped with state-of-the-art proven treatment so far. The could be included in international technical positions at world- vaccine products. For instance, these vaccines utilizing its Among these, six are still in pre- commonly used DT and TT animal research facilities and outbreak of Ebola virus in West emergency vaccine stockpiles. renowned pharmaceutical in using pneumococcal proteins core technologies, which clinical stage, including vaccine carrier proteins, and CRM197, has built pilot and commercial Africa in 2014-16 killed more Yu Xuefeng, chairman and companies abroad, CanSinoBIO or virulence factors to reduce the significantly improve the candidates for adenovirus, CanSinoBIO has developed manufacturing facilities to than 11,000 people.
    [Show full text]
  • En Este Número
    Boletín Científico No. 18 (1-10 julio/2021) EN ESTE NÚMERO VacCiencia es una publicación dirigida a Resumen de candidatos vacu- investigadores y especialistas dedicados a nales contra la COVID-19 ba- la vacunología y temas afines, con el ob- sadas en la plataforma de sub- jetivo de serle útil. Usted puede realizar unidad proteica en desarrollo a sugerencias sobre los contenidos y de es- nivel mundial. (segunda parte) ta forma crear una retroalimentación Artículos científicos más que nos permita acercarnos más a sus recientes de Medline sobre necesidades de información. vacunas. Patentes más recientes en Patentscope sobre vacunas. Patentes más recientes en USPTO sobre vacunas. 1| Copyright © 2020. Todos los derechos reservados | INSTITUTO FINLAY DE VACUNAS Resumen de vacunas contra la COVID-19 basadas en la plataforma de subunidad proteica en desarrollo a nivel mundial (segunda parte) Las vacunas de subunidades antigénicas son aquellas en las que solamente se utilizan los fragmentos específicos (llamados «subunidades antigénicas») del virus o la bacteria que es indispensable que el sistema inmunitario reconozca. Las subunidades antigénicas suelen ser proteínas o hidratos de carbono. La mayoría de las vacunas que figuran en los calendarios de vacunación infantil son de este tipo y protegen a las personas de enfermedades como la tos ferina, el tétanos, la difteria y la meningitis meningocócica. Este tipo de vacunas solo incluye las partes del microorganismo que mejor estimulan al sistema inmunitario. En el caso de las desarrolladas contra la COVID-19 contienen generalmente, la proteína S o fragmentos de la misma como el Dominio de Unión al Receptor (RBD, por sus siglas en inglés).
    [Show full text]
  • Management of COVID-19 a Handbook for Family Physicians
    Management of COVID-19 A Handbook for Family Physicians Dr. Alok Sharma, MS, Mch Dr. Hemangi Sane, MD, (Internal Medicine) Dr. Nandini Gokulchandran, MD Dr. Balaji Tuppekar, MD (Pulmonary Medicine) Dr. Prakash Gote, DA Ms. Pooja Kulkarni, M.Sc. Scientic and Editorial Co-ordinator Dr. Apeksha Kalvit, B.P.T., M.P.T. (Neuro-Paediatric) Physiotherapist NeuroGen DCH & KLS Wellness Institute Publication Navi Mumbai, Maharashtra, India. www.neurogenbsi.com Management of COVID-19 1 Management of COVID-19 A Handbook for Family Physicians © 2021 by NeuroGen Brain and Spine Institute All rights reserved. This book is protected by copyright. No part of this book may be reproduced in any form by any means, including photocopying, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for the brief quotations embodied in critical articles and reviews. This book is basically a compilation of information / literature on the available on the topic, from various sources (which have been acknowledged duly). However, this is by no means an exhaustive resource, since the eld is evolving at a very rapid pace. Every effort is made to ensure accuracy of material, but the publisher, printer and author will not be held responsible for any inadvertent error(s). Published by NeuroGen DCH, Navi Mumbai, India Cover Page by John Julius Printed by Surekha Press, A-20, Shalimar Industrial Estate, Matunga Labour Camp, Mumbai 400 019. Tel.: 2409 3877, 2404 3877 2 Management of COVID-19 Management of COVID-19 3 CONTENTS Section (A) - About Covid 1. Introduction Chapter for Book Management of COVID for family physicians................................................................................................
    [Show full text]
  • Heterologous Prime-Boost COVID-19 Vaccination: Initial Reactogenicity Data
    Correspondence Heterologous (100 participants with additional 24 (21%) of 112 recipients of BNT for prime-boost COVID-19 visits), at baseline (before the prime both prime and boost (difference 21%, dose), at day 28 (before the boost 95% CI 8–33%). Similar increases were Published Online vaccination: initial dose) and 7 days post-boost, graded observed for chills, fatigue, headache, May 12, 2021 https://doi.org/10.1016/ according to a modified US Food joint pain, malaise, and muscle ache reactogenicity data S0140-6736(21)01115-6 and Drug Administration toxicity (figure; appendix). There were no There is significant international scale (appendix). All analyses are hospitalisations due to solicited See Online for appendix interest in heterologous prime-boost descriptive, as the study was not symptoms, and most of this increase in COVID-19 vaccination to mitigate powered for reactogenicity, with reactogenicity was observed in the 48 h against supply shocks or shortages endpoints reported as frequencies and after immunisation (appendix). that might otherwise reduce the speed percentages, together with absolute Participants were advised that of vaccine roll-out. Additionally, in differences between heterologous and paracetamol might reduce vaccine light of changing recommendations homologous vaccine schedules and side-effects but were not actively coun- regarding use of the ChAdOx1 nCoV-19 corresponding 95% CIs. selled to medicate prophylactically. (ChAd) COVID-19 vaccine (Vaxzevria, Recruitment commenced on Paracetamol use in the 48 h post-boost AstraZeneca), several countries are now Feb 11, 2021, and was completed on vaccine was reported by 40 (36%) of advising that individuals previously Feb 26, 2021, with 830 participants 112 recipients of ChAd for both prime primed with this vaccine should now enrolled and randomised from and boost, 63 (57%) of 110 recipients receive an alternative vaccine as 978 screened (the CONSORT flow of ChAd for prime and BNT for boost, their second dose, most commonly diagram is available in the appendix).
    [Show full text]
  • Immunogenicity and Reactogenicity of a Heterologous COVID-19 Prime-Boost Vaccination Compared with Homologous Vaccine Regimens
    medRxiv preprint doi: https://doi.org/10.1101/2021.06.13.21258859; this version posted June 15, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Immunogenicity and reactogenicity of a heterologous COVID-19 prime-boost vaccination compared with homologous vaccine regimens Tina Schmidt1, Verena Klemis1,§, David Schub1,§, Janine Mihm2, Franziska Hielscher1, Stefanie Marx1, Amina Abu-Omar1, Sophie Schneitler3, Sören L. Becker3, Barbara C. Gärtner3, Urban Sester2, and Martina Sester1;* 1Department of Transplant and Infection Immunology, 2Department of Internal Medicine IV, 3Institute of Medical Microbiology and Hygiene, Saarland University, 66421 Homburg, Germany. §these authors contributed equally *Correspondence: Martina Sester, PhD, Saarland University, Department of Transplant and Infection Immunology, Institutes of Infection Medicine, building 47, Kirrberger Straße, D- 66421 Homburg, Germany; email: [email protected] Abstract Heterologous priming with the ChAdOx1-nCoV-19 vector-vaccine followed by boosting with an mRNA-vaccine is currently recommended in Germany, although data on immunogenicity and reactogenicity are not available. Here we show that the heterologous regimen induced spike-specific IgG, neutralizing antibodies, and spike-specific CD4 T-cells, which were significantly more pronounced than after homologous vector boost, and higher or comparable in magnitude to the homologous mRNA regimens. Moreover, spike-specific CD8 T-cell levels after heterologous vaccination were significantly higher than after both homologous regimens. Cytokine expression profiling showed a predominance of polyfunctional T-cells expressing IFNγ, TNFα and IL-2 with subtle differences between regimens.
    [Show full text]