Development of Vaccines Against Zika Virus

Total Page:16

File Type:pdf, Size:1020Kb

Development of Vaccines Against Zika Virus Review Development of vaccines against Zika virus Gregory A Poland, Richard B Kennedy, Inna G Ovsyannikova, Ricardo Palacios, Paulo Lee Ho, Jorge Kalil Zika virus is an emerging pathogen of substantial public health concern to human beings. Although most infections are Lancet Infect Dis 2018; asymptomatic or present with benign, self-limited symptoms, a small percentage of patients have complications, such 18: e211–19 as congenital anomalies in the developing fetus of pregnant women infected with the virus and neurological Published Online complications (eg, Guillain-Barré syndrome). To date, there is no vaccine, antiviral drug, or other modality available to January 25, 2018 http://dx.doi.org/10.1016/ prevent or treat Zika virus infection. In this Review, we examine vaccine development efforts for Zika virus to date and S1473-3099(18)30063-X research gaps in the development of candidate vaccines against Zika virus. Top research priorities should include Mayo Clinic Vaccine Research development of a better understanding of immunity to Zika virus to establish clear correlates of protection; determination Group, Mayo Clinic, Rochester, of what effect, if any, Zika vaccine-induced immune responses will have on subsequent dengue virus infection; MN , USA (Prof G A Poland MD, evaluation of vaccine immunogenicity and efficacy in healthy adults and in the various subpopulations affected by Zika Prof R B Kennedy PhD, Prof I G Ovsyannikova PhD); virus infection (children, pregnant women, women of childbearing age, and eldery people); and identification of the Instituto Butantan, São Paulo, molecular mechanisms that underlie birth defects and neurological sequelae related to Zika virus. Brazil (R Palacios MD, P L Ho PhD); and Medical School Introduction Review, we evaluate those efforts and outline scientific, and Heart Institute, University of São Paulo, São Paulo, Brazil Sometime in the early 1900s, probably in Uganda, the regulatory, and ethical issues related to the development (Prof J Kalil MD) ancestral Zika virus emerged and went undetected for of a vaccine against Zika virus. Correspondence to: decades. It was not until 1947, when sentinel rhesus Dr Gregory A Poland, Mayo monkey number 776 had a febrile illness, that researchers Zika virus Vaccine Research Group, looking for the yellow fever virus at the Ugandan Viral Zika virus is an arbovirus that belongs to the Flaviviridae Mayo Clinic, Rochester, 1 MN 55905, USA Research station identified Zika virus. Ugandans from family, which includes dengue, West Nile, and yellow fever [email protected] four different locations were studied and six (6·1%) of viruses. Zika virus has a single-stranded, positive sense 99 were positive for antibodies to the virus. At the time, RNA genome that encodes structural (capsid, precursor the importance of this emerging virus was unknown membrane [prM], and envelope [E]) and non-structural and unanticipated. The response to Zika virus as a proteins (1, 2A, 2B, 3, 4A, 4B, and 5). The genome is curiosity was justified, because at the time there were no translated as a single polyprotein and then is proteolytically known infections or outbreaks of importance in human cleaved into individual proteins. The prM, E, and non- beings. structural protein 1 have the greatest sequence divergence The first human case of Zika infection was reported in from other flaviviruses. Three main lineages of Zika virus 1952.2 Although Zika infection had been reported a decade have been found, east African, west African, and Asian. earlier,3,4 this infection was later identified as Spondweni These strains might be differentially associated with the virus.5 Other isolated cases of Zika infection were reported neurological defects seen during the outbreaks in the through the 1960s and 1970s.1,6 Nonetheless, Zika virus was Pacific and South America. Strains from Polynesia and not recognised as a human pathogen of importance until South America have high degrees of similarity (about 2007, when an outbreak of rash and fever occurred on Yap 99% sequence identity),9 while strains from the western Islands and led to 49 confirmed—and 59 probable—cases hemisphere are about 89% identical to the African of Zika virus infection in human beings.7 At the time, a genotypes.10 household survey of 557 people revealed that 412 (74%) had The virus was first isolated from rhesus macaques and antibodies for Zika virus. A larger second outbreak was subsequently found in mosquito vectors (including occurred in 2013–14 in French Polynesia, involving Aedes aegypti, Anopheles spp, and Mansonia spp).1 Specific 333 confirmed cases and 19 000–32 000 suspected cases.8 antibodies against Zika virus have been found in sheep, For the first time, Guillain-Barré syndrome was observed cows, goats, horses, water buffalo, ducks, rodents, bats, in conjunction with these infections. During the non-human primates, and other wild animals.11–17 This 2014–15 outbreaks of Zika virus in Brazil, public health large and diverse pool of animal hosts facilitates the authorities reported a noticeable increase in children born spread of the virus and can contribute to the emergence with microcephaly. of recombinant strains. Since 2007, local transmission has been documented in Barba-Spaeth and colleagues18 studied the crystal 52 countries and territories, including in continental structure of the Zika virus E protein complexed to USA. Despite the scale of the outbreak, it was not until two cross-reactive antibodies specific for dengue virus, February, 2016, that WHO declared Zika virus to be a which provided important data on conserved epitopes Public Health Emergency of International Concern. targeted by cross neutralising antibodies. Since then, the Before this announcement, there were no known efforts crystal structures of the mature19 and immature20 Zika to develop a vaccine against the Zika virus. Since then, virus have been resolved, allowing us to evaluate the researchers in this field have tried to understand Zika effect of mutations that have occurred since the start of virus and to develop a vaccine against Zika virus. In this the epidemic, to identify conserved regions with other www.thelancet.com/infection Vol 18 July 2018 e211 Review flaviviruses, to map neutralising epitopes, and to better Zika virus is mostly suppressed. As a result, sexual understand viral attachment and entry. transmission of the virus has been documented,33,34 and perinatal transmission has been described during Zika virus infection pregnancy.35,36 Thus, vaccines and treatments designed to Zika virus, which has rapidly emerged as a threat to fight Zika virus infection in all organs is an important public health, is transmitted by A aegypti mosquitoes.21 consideration in vaccine development. An improved Zika virus spread beyond its historical range in equatorial understanding of interactions between the virus and host Africa and Asia to the Federated States of Micronesia will inform the public health response to this pathogen. (Yap Islands). In 2015, the virus spread to the Caribbean, South America, and Central America, where it has Immune responses to Zika virus caused epidemics.22 22·7 million people in the USA live Many cellular proteins could act as potential entry receptors in areas with active mosquito populations that are (dendritic-cell-specific ICAM-3 grabbing non-integrin, conducive to year-round transmission of Zika virus.23 The Axl receptor tyrosine kinase, hepatitis A virus cellular Aedes species of mosquitoes known to transmit Zika receptor 1, tyrosine protein kinase 3).37,38 Cellular infection virus—A aegypti and A albopictus—are present in more with Zika virus is characterised by expression of Toll-like than 30 states and territories in the USA. Furthermore, receptor 3, retinoic acid inducible gene-I, and melanoma 60% of people in the USA live in areas that might allow differentiation associated gene 5, secretion of type 1 seasonal transmission of Zika virus due to the and type 2 interferons, and upregulation of interferon- geographical distribution of Aedes spp mosquitos.23 The stimulated genes that mediate antiviral responses (OAS2, mosquito vectors carrying Zika virus are expanding in ISG15, or MX1).38 Glycosaminoglycans can aid the geographical location, and currently cover Africa, South attachment and entry of Zika virus.39 and Central America, India, Singapore, Puerto Rico, and Initial reports indicated that immune responses to the USA, and will probably spread to other parts of Asia.24 Zika virus were similar to that of other flaviviruses in that As of March 10, 2017, people in 84 countries and neutralising antibodies (primarily directed at E protein) territories had been infected with Zika virus.25 are thought to play a major part in protection against 80% of Zika virus infections are asymptomatic, while infection.40–43 In fact, there is considerable serological the other 20% of infections typically present as a mild crossreactivity between Zika virus and other flaviviruses, form of dengue-like disease with mild fever, skin rash, and this reactivity has hindered the use of diagnostic muscle and joint pain, conjunctivitis, vomiting, tests and seroprevalence studies in geographical areas headache, malaise, prostration, and oedema of the hands where antibody responses to other flaviviruses are also and feet.26 These symptoms usually last for 2–7 days, and present.1,44 In some geographical areas, monoinfection the incubation period of Zika virus typically ranges from with Zika virus is less common than co-infection
Recommended publications
  • February 17, 2021
    January 30 – February 17, 2021 This weekly science review is a snapshot of the new and emerging scientific evidence related to COVID-19 during the period specified. It is a review of important topics and articles, not a guide for policy or program implementation. The findings captured are subject to change as new information is made available. We welcome comments and feedback at [email protected]. In depth: Should second doses of COVID-19 vaccines be delayed? Main message: While the rollout of multiple vaccines has offered hope to control or end the COVID-19 pandemic, global vaccine demand will continue to outpace supply for the foreseeable future. To date, people in 130 countries have not yet received a single dose of COVID-19 vaccine. In countries where vaccination has begun, limited supplies of vaccine in combination with surges in cases and deaths have overwhelmed health care systems. Further, the emergence of more transmissible SARS-CoV-2 variants has led many to question existing vaccine rollout plans and propose alternative strategies. Some countries and experts have recommended delaying second doses of vaccine to maximize the number of people who receive at least one dose. This raises a critical question: What do we know about vaccines, especially the vaccines for COVID-19, that may allow flexibility in vaccine schedules? This is a complex question and there may not be a straightforward answer. Our knowledge is evolving rapidly as vaccine trials progress and rollout continues, and we must keep in mind that different approaches to vaccine scheduling may be appropriate in different settings.
    [Show full text]
  • ADVISORY COMMISSION on CHILDHOOD VACCINES TABLE of CONTENTS December 8, 2017
    ADVISORY COMMISSION ON CHILDHOOD VACCINES TABLE OF CONTENTS December 8, 2017 TAB • ACCV Agenda 1 • ACCV Charter • ACCV Roster • 2017 Meeting Dates • Meeting Minutes 2 o Draft Minutes – September 8, 2017 • Vaccine Injury Compensation Trust Fund Statement 3 o Vaccine Injury Compensation Trust Fund Summary Sheet for the Period of 10/1/2016 – 9/30/2017 • VICP Data and Statistics 4 • Meeting Presentations & Updates 5 o Report from the Division of Injury Compensation Programs 5.1 o Report from the Department of Justice 5.2 o Petitions to Add Injuries to the Vaccine Injury Table Introduction 5.3 o Petition to Add Tics as an Injury to the Vaccine Injury Table 5.4 o Petition to Add Asthma as an Injury to the Vaccine Injury Table 5.5 5.6 o Petition to Add Pediatric Autoimmune Neuropsychiatric Syndrome (PANS), Pediatric Infection-Triggered Autoimmune Neuropsychiatric Disorders (PITANDS), and Pediatric Autoimmune Neuropsychiatric Disorders (PANDAS) as Injuries to the Vaccine Injury Table o Petition to Add Experimental Autoimmune Encephalomyelitis (EAE) and/or 5.7 Acute Demyelinating Encephalomyelitis (ADEM) as injuries to the Vaccine Injury Table 5.8 o Update on the Immunization Safety Office Vaccine Activities (CDC) o Update on the National Institute of Allergy and Infectious Diseases Vaccine 5.9 Activities (NIH) o Update on the Center for Biologics, Evaluation and Research Vaccine 5.10 Activities (FDA) 5.11 o Update from the National Vaccine Program Office • Program Related Articles 6 6.1 o Popular Science, “Why Are We So Bad At Producing The Right
    [Show full text]
  • COVID-19 Vaccine: Critical Questions with Complicated Answers
    Review Biomol Ther 29(1), 1-10 (2021) COVID-19 Vaccine: Critical Questions with Complicated Answers Mohammad Faisal Haidere1,†, Zubair Ahmed Ratan2,3,†, Senjuti Nowroz4, Sojib Bin Zaman5, You-Jung Jung6, Hassan Hosseinzadeh2,* and Jae Youl Cho7,* 1Department of Soil, Water and Environment, University of Dhaka, Dhaka 1000, Bangladesh 2School of Health & Society, University of Wollongong, NSW 2500, Australia 3Department of Biomedical Engineering, Khulna University of Engineering and Technology, Khulna 9203, Bangladesh 4Department of Chemistry, University of Dhaka, Dhaka 1000, Bangladesh 5Department of Medicine, School of Clinical Sciences, Monash University, Victoria 3800, Australia 6Biological Resources Utilization Department, National Institute of Biological Resources, Incheon 22689, Republic of Korea 7Department of Integrative Biotechnology, and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea Abstract COVID-19 has caused extensive human casualties with significant economic impacts around the globe, and has imposed new challenges on health systems worldwide. Over the past decade, SARS, Ebola, and Zika also led to significant concerns among the scientific community. Interestingly, the SARS and Zika epidemics ended before vaccine development; however, the scholarly com- munity and the pharmaceutical companies responded very quickly at that time. Similarly, when the genetic sequence of SARS- CoV-2 was revealed, global vaccine companies and scientists have stepped forward to develop a vaccine, triggering a race toward vaccine development that the whole world is relying on. Similarly, an effective and safe vaccine could play a pivotal role in eradi- cating COVID-19. However, few important questions regarding SARS-CoV-2 vaccine development are explored in this review. Key Words: COVID-19, Vaccine, Vaccine backfires, Vaccine safety INTRODUCTION vember 2002 in the Guangdong province of China.
    [Show full text]
  • Scientific Consultation on Zika Virus Vaccine Development
    World Health Organization and National Institute of Allergy and Infectious Diseases, National Institutes of Health Scientific Consultation on Zika Virus Vaccine Development January 10–11, 2017 5601 Fishers Lane Rockville, Maryland Meeting Summary Tuesday, January 10, 2017 INTRODUCTION Anthony S. Fauci, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), United States The National Institute of Allergy and Infectious Diseases (NIAID) and the World Health Organization (WHO) convened the Scientific Consultation on Zika Virus Vaccine Development to discuss challenges and recent advances in the development of Zika virus (ZIKV) vaccines. The NIAID Director opened the meeting by stating that the recent spread of ZIKV mirrors that of other emerging arboviruses in the Americas in the past several years, including chikungunya, West Nile, and dengue. The NIAID research response to Zika builds on those experiences. A primary goal of this research is to develop medical countermeasures including diagnostics, therapeutics, and vaccines. Challenges specific to the development of a Zika vaccine include: the lack of adequate animal models; uncertainties in the epidemiology, which affect clinical trial site selection; the likelihood that the vaccine will need to induce sterilizing immunity to prevent congenital Zika syndrome (CZS); preexisting immunity to other flaviviruses in some regions; and potential specific risks such as Guillain-Barré syndrome (GBS) and the administration of live vaccines to pregnant women. Several Zika vaccine candidates are being developed with different development timelines and likely target populations. The planned timelines include large, well-controlled clinical trials to evaluate safety and efficacy, and if successful, subsequent licensure; should public health need and available safety and efficacy data justify deployment of vaccine before licensure, access through appropriate regulatory mechanisms could be considered.
    [Show full text]
  • Zika Vaccine Development Technology Roadmap April 2019
    Zika Vaccine Development Technology Roadmap April 2019 Acknowledgements This work was built on critical input from the WHO Zika vaccine technical roadmap advisory group members in 2017 who worked primarily on Zika vaccines for outbreak use: Alan Barrett, University of Texas Medical Branch, USA; Amy Lambert, Centers for Diseases Control and Prevention, Fort Collins, USA; Anna Durbin, Johns Hopkins University, Baltimore, USA; David C. Kaslow, PATH, Seattle, USA; Heidi Meyer, PEI, Germany; Carlos Pardo-Villamizar, Neuroviruses Emerging in the Americas Study (NEAS), Colombia and Johns Hopkins University, Baltimore, USA; Laura C. Rodrigues, London School of Hygiene and Tropical Medicine, UK, and Microcephaly Epidemic Research Group (MERG), Brazil; Stephen J. Thomas, State University of New York Upstate Medical University, Syracuse, USA; Wellington Sun, US Food and Drug Administration, USA. The work on Zika vaccines for endemic use was further developed in 2018 and 2019 by: Alan Barrett, University of Texas Medical Branch, USA; Cristina Cassetti, NIH/NIAID, USA; Anna Durbin, Johns Hopkins University, Baltimore, USA; David C. Kaslow, PATH, Seattle, USA; Heidi Meyer, PEI, Germany; Eng-Eong Ooi, Duke-NUS, Singapore; Alexander Precioso, Clinical Trials and Pharmacovigilance Division, Butantan, Brazil; Stephen J. Thomas, State University of New York Upstate Medical University, Syracuse, USA; In-Kyu Yoon, International Vaccine Institute Seoul, South Korea. We are grateful to all individuals and represented institutions that contributed to the discussions at the WHO consultation meetings on Zika Virus vaccine development, and to the members of the WHO Product Development for Vaccines Advisory Committee (http://www.whoint/immunization/research/committees/pdvac). WHO gratefully acknowledges the many individuals and institutions that provided comments to this document during the public consultation.
    [Show full text]
  • In the News 2016 - 2017 TABLE of CONTENTS
    In the News 2016 - 2017 TABLE OF CONTENTS Protein Sciences press release 8 June 22, 2017 Superior Protection by Flublok® Influenza Vaccine in Seniors Documented in New England Journal of Medicine Protein Sciences press release 10 April 19, 2017 Peer-reviewed Publication Confirms the Absence of Rhabdovirus in Cell Line Used for Manufacturing of Flublok Protein Sciences press release 12 April 4, 2017 Flublok Quadrivalent Influenza Vaccine Adds a 9-Month Shelf Life to Its List of Benefits Protein Sciences press release 14 March 21, 2017 Protein Sciences Gears Up to Combat Pandemic Influenza Due to Recent Outbreaks in China Protein Sciences press release 16 February 22, 2017 Protein Sciences and Partnership for Influenza Vaccine Introduction (PIVI) Team Up to Combat the Flu in Mongolia Protein Sciences press release 18 January 12, 2017 U.S. Protein Sciences’ Zika Vaccine Shows Good Results in Preclinical Testing: Bio-Manguinhos/ Fiocruz Joins International Consortium Fierce Pharma 20 December 1, 2016 Small flu vax players poised to win ‘sizable’ share of market, firm predicts TABLE OF CONTENTS Protein Sciences press release 6 November 11, 2016 Flublok® Influenza Vaccine Now Available in Mexico Fierce Pharma 8 October 17, 2016 Protein Sciences CEO Eyes GSK, Sanofi goliaths in fight to ‘take over’ quadrivalent flu vax market Protein Sciences press release 10 October 11, 2016 FDA Approves Flublok® Quadrivalent Flu Vaccine Protein Sciences press release 12 September 22, 2016 Protein Sciences and Avanzcare Announce Licensing of Influenza Vaccines
    [Show full text]
  • Efficacy of a T Cell-Biased Adenovirus Vector As a Zika Virus Vaccine
    University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Virology Papers Virology, Nebraska Center for 12-20-2018 Efficacy of a T Cell-Biased Adenovirus Vector as a Zika Virus Vaccine Brianna L. Bullard University of Nebraska - Lincoln, [email protected] Brigette N. Corder University of Nebraska - Lincoln Matthew J. Gorman Washington University School of Medicine Michael S. Diamond Washington University School of Medicine Eric A. Weaver University of Nebraska-Lincoln, [email protected] Follow this and additional works at: https://digitalcommons.unl.edu/virologypub Part of the Biological Phenomena, Cell Phenomena, and Immunity Commons, Cell and Developmental Biology Commons, Genetics and Genomics Commons, Infectious Disease Commons, Medical Immunology Commons, Medical Pathology Commons, and the Virology Commons Bullard, Brianna L.; Corder, Brigette N.; Gorman, Matthew J.; Diamond, Michael S.; and Weaver, Eric A., "Efficacy of a T Cell-Biased Adenovirus Vector as a Zika Virus Vaccine" (2018). Virology Papers. 383. https://digitalcommons.unl.edu/virologypub/383 This Article is brought to you for free and open access by the Virology, Nebraska Center for at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Virology Papers by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. www.nature.com/scientificreports OPEN Efcacy of a T Cell-Biased Adenovirus Vector as a Zika Virus Vaccine Received: 7 August 2018 Brianna L. Bullard 1, Brigette N. Corder1, Matthew J. Gorman2, Michael S. Diamond 2 & Accepted: 10 November 2018 Eric A. Weaver1 Published: xx xx xxxx Zika virus (ZIKV) is a major public health concern due to the risk of congenital Zika syndrome in developing fetuses and Guillain-Barre syndrome in adults.
    [Show full text]
  • Directory 2017.Pdf
    Dear Colleagues and Friends, It gives me immense pleasure to connect with you on the occasion of the 18th Annual General Meeting (AGM) of DCVMN. I would like to take this opportunity to reiterate my gratefulness to you - our Members - to have elected me as President to represent not only a group of extraordinary professionals, but also a Network of companies with global impact. I am honoured and humbled that you have placed your trust in me. I am confident that with your cooperation and support we would certainly take this organisation to the next level. DCVMN and its members are continuously recognized as key players in global health, particularly in tackling emerging outbreaks, elimination of tetanus and measles/rubella and in the eradication of Polio virus. We are proud of what we have been able to accomplish over the years, enabling our Network to demonstrate dynamic growth and to engage in supporting several global health efforts, particularly in protecting people from infectious diseases in developing countries by supplying high-quality, affordable vaccines around the world. Since its inception in 2000, DCVMN has grown at a fast pace and today represents more than 50 vaccine manufacturers. Still we have a long way to go. The current AGM is a great platform for us to ponder upon our priorities and challenges as developing countries manufacturers and also scope out our activities as a network and work towards more effective organizational strategies for the coming years. We must leverage our collective knowledge and organizational experience to bring actionable ideas to the table at this AGM.
    [Show full text]
  • Zika Virus Research and Development (R&D) Roadmap
    ZIKV R&D Roadmap v7.1 DRAFT FOR PUBLIC COMMENT February 2021 1 Zika Virus Research and Development (R&D) Roadmap 2 3 Roadmap purpose: To provide a 10-year framework for prioritizing research activities aimed at 4 advancing the development, licensure, manufacture, deployment, and assessment of medical 5 countermeasures (MCMs)—diagnostics, therapeutics, and vaccines—against Zika virus (ZIKV) disease. By 6 highlighting key knowledge gaps, identifying strategic goals and milestones, and encouraging synergistic 7 research and development (R&D) activities, the roadmap will serve as a valuable tool to advance the 8 existing complex field of ZIKV MCM research and stimulate overall investment in R&D and in 9 implementation activities. 10 11 Vision statement: To ensure that robust MCMs to detect, prevent, and control human ZIKV clinical 12 disease, including congenital anomalies and neurodevelopmental disabilities associated with congenital 13 ZIKV infection, are readily available and accessible for use in areas of known or potential ZIKV 14 transmission. These MCMs include: (1) accurate, standardized, and validated diagnostics; (2) safe and 15 effective treatments aimed primarily at preventing congenital ZIKV infection; and (3) safe and effective 16 vaccines to prevent disease, disability, and death. 17 18 INTRODUCTION 19 ZIKV is a mosquito-borne flavivirus that was first isolated in 1947 from a sentinel rhesus monkey in the 20 Zika Forest of Uganda (Dick 1952). Only a handful of ZIKV disease cases in humans had been identified 21 prior to a 2007 outbreak in the State of Yap, Federated States of Micronesia, during which an estimated 22 73% of the population was infected (Duffy 2009, Petersen 2016).
    [Show full text]
  • Considerations for Bioanalytical Characterization and Batch Release of COVID-19 Vaccines ✉ Gautam Sanyal 1 , Anna Särnefält 1 and Arun Kumar 1
    www.nature.com/npjvaccines PERSPECTIVE OPEN Considerations for bioanalytical characterization and batch release of COVID-19 vaccines ✉ Gautam Sanyal 1 , Anna Särnefält 1 and Arun Kumar 1 The COVID-19 pandemic has prompted hundreds of laboratories around the world to employ traditional as well as novel technologies to develop vaccines against SARS-CoV-2. The hallmarks of a successful vaccine are safety and efficacy. Analytical evaluation methods, that can ensure the high quality of the products and that can be executed speedily, must be in place as an integral component of Chemistry, Manufacturing, and Control (CMC). These methods or assays are developed to quantitatively test for critical quality attributes (CQAs) of a vaccine product. While clinical (human) efficacy of a vaccine can never be predicted from pre-clinical evaluation of CQA, precise and accurate measurements of antigen content and a relevant biological activity (termed “potency”) elicited by the antigen allow selection of potentially safe and immunogenic doses for entry into clinical trials. All available vaccine technology platforms, novel and traditional, are being utilized by different developers to produce vaccines against SARS-CoV-2. It took less than a year from the publication of SARS-CoV-2 gene sequence to Emergency Use Authorization (EUA) of the first vaccine, setting a record for speed in the history of vaccine development. The largest ever global demand for vaccines has prompted some vaccine developers to enter multiple manufacturing partnerships in different countries in addition to implementing unprecedented scale-up plans. Quantitative, robust, and rapid analytical testing for CQA of a product is essential in ensuring smooth technology transfer between partners and allowing analytical bridging between vaccine batches used in different 1234567890():,; clinical phases leading up to regulatory approvals and commercialization.
    [Show full text]
  • Mrna Vaccines Against Flaviviruses
    Review mRNA Vaccines against Flaviviruses Clayton J. Wollner and Justin M. Richner * Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612, USA; [email protected] * Correspondence: [email protected] Abstract: Numerous vaccines have now been developed using the mRNA platform. In this approach, mRNA coding for a viral antigen is in vitro synthesized and injected into the host leading to exoge- nous protein expression and robust immune responses. Vaccines can be rapidly developed utilizing the mRNA platform in the face of emerging pandemics. Additionally, the mRNA coding region can be easily manipulated to test novel hypotheses in order to combat viral infections which have remained refractory to traditional vaccine approaches. Flaviviruses are a diverse family of viruses that cause widespread disease and have pandemic potential. In this review, we discuss the mRNA vaccines which have been developed against diverse flaviviruses. Keywords: flavivirus; mRNA vaccines; Dengue; Zika; tick-borne encephalitis 1. Introduction Flaviviridae is a diverse family of positive sense, RNA viruses that are spread predom- inantly by arthropod vectors [1]. Outbreaks of flaviviruses across the globe have plagued humankind for centuries [2]. Even in modern times, flaviviral outbreaks can lead to global pandemics as demonstrated after the introduction and subsequent spread of West Nile virus Citation: Wollner, C.J.; Richner, J.M. into North America in 1999 and more recently, the emergence of Zika virus into the Western mRNA Vaccines against Flaviviruses. Hemisphere in 2013 [3]. One of the most successful early vaccination campaigns ever Vaccines 2021, 9, 148. https:// was against the flavivirus yellow fever virus in the 1930’s [4].
    [Show full text]
  • Frequently Asked Questions About COVID-19 Candidate Vaccines and Access Mechanisms
    Frequently Asked Questions about COVID-19 Candidate Vaccines and Access Mechanisms Version 3, 6 January 20211,2 Progress in the Development of COVID-19 Vaccines 1. Is there a vaccine against COVID-19? As of January 6th, 2021, there are some COVID-19 vaccines for which certain national regulatory authorities have authorized the use. The World Health Organization (WHO) has also granted Emergency Use Listing (EUL) authorization to the Pfizer/BioNTech vaccine3. The following vaccines have received national regulatory authorization3,4: ● Moderna/ NIAID/ Lonza/ Catalent/ Rovi/ Medidata/ BIOQUAL: Authorized for "emergency use" in the United States (U.S.). ● BioNTech/ Pfizer/ Fosun Pharma/ Rentschler Biopharma: Authorized for use by the European Commission and in the U.S., Mexico, Saudi Arabia, Canada, Bahrain, and the United Kingdom (U.K.). ● Gamaleya Research Institute: as a "registered" vaccine by the Russian Ministry of Health ● CanSino Biologics/ Beijing Institute of Biotechnology/ Petrovax: for "the military" by China’s Central Military Commission. ● Wuhan Institute of Biological Products/ Sinopharm: for "emergency use" in China and the United Arab Emirates. ● Sinovac/ Instituto Butantan/ Bio Farma: for "emergency use" in China. ● Beijing Institute of Biological Products/ Sinopharm: for "emergency use" in China and the United Arab Emirates. As of January 6th, 2021, there are 63 candidate vaccines in clinical evaluation in humans, and 172 candidate vaccines in the preclinical phase5. 1 Document subject to revision as new evidence and information become available. 2 A previous version of the document was published on 27 August 2020: Pan American Health Organization. Frequently Asked Questions (FAQs) about COVID-19 Candidate Vaccines and Access Mechanisms [Internet].
    [Show full text]