Fundraising net proceeds go to COVID-19 Solidarity Response Fund for WHO

The Race for COVID-19 Vaccines: A Brief Overview

Vaccines save millions of lives each year from various illnessness1. As we near one year completion mark of the COVID-19 pandemic there have been over 63 million global infections and over 1.4 million deaths2. The consensus among experts is that only an effective vaccine will end this pandemic. Vaccine developers are making rapid progress toward developing a safe and effective vaccine against SARS-CoV-2, the novel coronavirus which causes COVID-19. Data from phase 1 and phase 2 trials are already available for several vaccine candidates, and many have moved into phase 3 trials3 with preliminary results announced in just the last few weeks4-6. Pfizer4, Moderna5, and AstraZeneca6 reported minimal side effects for their vaccines with efficacy rates up to 95% and it is now a matter of weeks-months when these vaccines will become available.

Types of vaccine in development

In general, the vaccine technologies can be divided into ‘traditional’ (live-attenuated or inactivated virus vaccines), recombinant protein and viral vector, and next-generation RNA and DNA approaches7,8.

Live-attenuated vaccines

Live-attenuated vaccines are produced by generating a attenuated version of the virus that does not cause the disease but induces the same immune responses as natural infection. Although live vaccines tend to create strong long-lasting immune response, these vaccines are not recommended for immunocompromised individuals since it is possible for attenuated viruses to cause disease progression in these individuals. As of date, only three live-attenuated vaccines are currently in preclinical evaluation3.

Inactivated virus vaccines

Inactivated vaccines are produced by growing SARS-CoV-2 in cell culture followed by complete inactivation. They can induce a strong antibody response but require large quantities of virus and biosafety containment level 3 large-scale virus production facilities. Several versions of inactivated SARS-CoV-2 have entered clinical trials, with four candidates in phase 3 trials3.

Recombinant protein vaccines

For coronavirus, recombinant protein vaccines are commonly based on the spike protein, a protein present on the surface of the virus that mediates entry into the host cell by binding to the ACE-2 receptor, which is present on human endothelial cells. Other recombinant protein vaccines include receptor-binding domain (RBD) and virus-like particle (VLP) based vaccines. The advantage of recombinant protein vaccines is that they can be produced without handling a live virus and may have fewer side effects than an intact virus. However, such vaccines can also have disadvantages. The spike protein is hard to express, and this is likely to have an impact on production yields. Also, these vaccines may be poorly immunogenic requiring adjuvants to stimulate a stronger immune response. There is only one protein-based vaccine candidate in phase 3 trials, but several others are in phase 1 and/or 2 trials3.

Viral vector vaccines

Viral vector vaccines offer a high level of protein expression, long-term stability and are capable of inducing strong immune responses.  These vaccines are typically based on a virus that does not cause human disease and that is engineered to express the SARS-CoV-2 spike protein. A disadvantage is that some of these viral vectors can be neutralized by pre-existing immunity against the viral vector. Several viral vector vaccine candidates have entered clinical trials, with four candidates in phase 3 trials3. Of those, promising early results from an interim analysis of vaccine candidates from AstraZeneca/University of Oxford was just announced6. There are two viral vector vaccines currently licensed, one from CanSino that is currently in use in the Chinese military, and another from Gamaleya Research Institute in Russia, which was licensed without a phase 3 trial7.

Nucleic acid vaccines

Nucleic acid (DNA and RNA) technologies are more recent and offer great flexibility in terms of antigen manipulation and potential for rapid development. However, nucleic acid vaccines may show low immunogenicity, and it is unclear what issues will be encountered in terms of long-term storage stability since they storage at extreme cold temperatures (£ 70° C). Several nucleic acid vaccine candidates (five DNA-based and six RNA-based candidates) have entered clinical trials. Primary efficacy analyses from phase 3 trials have shown that RNA-based vaccine candidates from Pfizer/BioNTech and Moderna/NIAID are safe and 95% effective and both companies have already applied for US and European emergency regulatory approval4,5. The UK regulator has just approved the Pfizer/BioNTech vaccine and the UK has become the first country in the world to approve the first COVID-19 vaccine.

Conclusion

More than 200 vaccine candidates, based on several different platforms, are currently in development against SARS-CoV-2 with 48 candidate vaccines already in phase 3 trials3. There are many different COVID-19 vaccines in development because it is not yet known which ones will be effective and safe and different vaccine types may be needed for different population groups. The World Health Organization (WHO) maintains a working document3 that includes most of the vaccines in development and is available at https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines.

About the author: 

Lúcia Moreira Teixeira is an expert in Immunology driven by a personal passion for science and the ambition to translate ground-breaking science into innovative life-changing immunotherapies. She is interested in immuno-oncology, autoimmune and infectious diseases. She strongly believes researchers should engage more in science communication. Find her on twitter – @LMTimmunol – or LinkedIn – www.linkedin.com/in/moreirateixeiralucia.

References

1. WHO. Vaccines and immunization. https://www.who.int/health-topics/vaccines-and-immunization

2. WHO Coronavirus Disease (COVID-19) Dashboard. (Accessed December 3, 2020). https://covid19.who.int/

3. WHO. Draft Landscape of COVID-19 Candidate Vaccines. (Publication of November 12, 2020). https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines

4. Pfizer November 18, 2020. Pfizer and BioNTech Conclude Phase 3 Study of COVID-19 Vaccine Candidate, Meeting All Primary Efficacy Endpoints. https://www.businesswire.com/news/home/20201118005595/en/

5. Moderna November 30, 2020. Moderna Announces Primary Efficacy Analysis in Phase 3 COVE Study for Its COVID-19 Vaccine Candidate and Filing Today with U.S. FDA for Emergency Use Authorization.

https://www.businesswire.com/news/home/20201130005506/en/

6. AstraZeneca November 23, 2020. AZD1222 vaccine met primary efficacy endpoint in preventing COVID-19. https://www.astrazeneca.com/media-centre/press-releases/2020/azd1222hlr.html

7. Krammer, F. SARS-CoV-2 vaccines in development. Nature 586, 516–527 (2020). https://doi.org/10.1038/s41586-020-2798-3

8. WHO. What we know about COVID-19 vaccine development (Publication 6 October 2020). https://www.who.int/publications/m/item/what-we-know-aboutcovid-19-vaccine-development

Share on linkedin
LinkedIn
Share on twitter
Twitter
Share on facebook
Facebook
Share on xing
XING
Share on email
Email

You may also be interested in...

James E. Crowe, Jr., MD,

Director, Vanderbilt Vaccine Center; Professor, Pediatrics and Pathology, Microbiology and Immunology, Ann Scott Carell Chair; Founder, IDBiologics

Dr. Crowe’s laboratory has a broad portfolio of work in the area of viral immunology and antibody sciences, with the goal to discover mechanisms of immunity important to developing new therapeutics and vaccines.

Dr. Crowe received his MD degree from the University of North Carolina at Chapel Hill, where he also completed his pediatrics residency. Following his clinical training, Dr. Crowe received five years of post-doctoral training in the laboratory of Infectious Diseases at the NIH. He completed infectious diseases fellowship training in 1996 at Vanderbilt and has run an independent laboratory at Vanderbilt since that time. He is currently Professor of Pediatrics and of Pathology, Microbiology and Immunology, and the Ann Scott Carell Chair, Vanderbilt University Medical Center. The laboratory’s work has been published in over 300 publications in high-quality science journals including CellScience and Nature, and leading medical journals including the New England Journal of Medicine and JAMA. Dr. Crowe was elected to the National Academy of Medicine in 2014 and the National Academy of Inventors in 2017. He has been the recipient of investigator awards from the March of Dimes, American Society for Microbiology, Pediatric Infectious Diseases Society, and Society for Pediatric Research. He was awarded the Judson Infectious Daland Prize of the American Philosophical Society, the Oswald Avery Award of the IDSA, the E. Mead Johnson Award for Excellence in Pediatrics, the Outstanding Investigator Award of the American Federation for Medical Research, the Norman J. Siegel Award of the American Pediatric Society, the Samuel Rosenthal Prize for Excellence in Academic Pediatrics, the Stanley J. Korsmeyer Award of American Society for Clinical Investigation, the Distinguished Medical Alumnus Award from UNC School of Medicine, Chapel Hill, NC. He is an elected Fellow of AAM, AAAS, ASCI, and AAP, IDSA, APS, and others. His research team was selected as the Best Academic Research Team at the 11th Annual Vaccine Industry Excellence Awards. He was awarded the inaugural 2019 Merck Future Insight Prize, a 1M Euro prize shared with Pardis Sabeti. 

He is the Founder of IDBiologics, Inc., an early-stage biotech company developing human monoclonal antibodies for infectious diseases.

Daniel Chen, MD, PhD

CMO, IGM Bioscience

Daniel S. Chen, MD, PhD, is the Chief Medical Officer for IGM Biosciences, and former Vice President, Global Head of Cancer Immunotherapy Development at Genentech/Roche.  He received a BS degree in Biology from the Massachusetts Institute of Technology (1990), a PhD in Microbiology & Immunology (1996), and MD (1998) from the University of Southern California. His PhD work and publications focused on “Early Events in Coronavirus Infection.”

Daniel completed an Internal Medicine Residency and Medical Oncology Fellowship at Stanford University (2003). He went on to complete a Post-doctoral fellowship with Mark Davis in Immunology, where he was a Howard Hughes Medical Institute Associate. He also ran the metastatic melanoma clinic at the Stanford Cancer Center from 2003-2006. In that time, he studied human anti-cancer immune responses pre- and post-cancer vaccination and cytokine administration to determine why anti-tumor immune responses were not more clinically effective. He received a U19 grant to develop better immunologic tools to interrogate human immune responses and ultimately patented the MHC cellular microarray to detect and functionally characterize antigen-specific T cell states.

He continued as Adjunct Clinical Faculty at Stanford from 2006-2016, where he cared for melanoma patients. At Genentech from 2006-2018, Daniel focused on the clinical development of anti-angiogenic and immune-modulatory targeted therapies in both early and late development, as well as the diagnostic tools to aid their development. This included leading the clinical development for atezolizumab, a PD-L1 inhibitor, from the time the program was in research through IND, Phase I, Phase II, Phase III, to filing and approvals in multiple indications worldwide. At IGM, Daniel focuses on the development of novel engineered multivalent and multispecific therapeutics. He is a reviewer for Nature, Immunity, and Clinical Cancer Research, serves on the Board of Directors for SITC, co-chair of the CRI cancer Immunotherapy consortium, gave the keynote presentation at the AACR NCI EORTC Annual Meeting 2014 and presented at the US Congressional Briefing on Immuno Oncology in 2017. He has continued to publish with academic and industry collaborators in the field of cancer immunotherapy, including the often-referenced Chen and Mellman manuscripts, “Elements of cancer immunity and the cancer-immune set point” and “Oncology meets Immunology: The Cancer-Immunity Cycle.”

Imre Berger

Founding Director, Max Planck Bristol Centre; Chair in Biochemistry and Chemistry; University of Bristol UK

Imre Berger was trained as a biochemist and synthetic biologist at Leibniz University and Medical School (MHH) in Hannover (Germany), at MIT (Cambridge, USA), and at ETH Zurich (Switzerland). Imre’s team develops enabling methods for DNA delivery and genome engineering, engineers synthetic vaccines and nanosensors and researches the structure and mechanism of multiprotein complexes in human health and disease. After Group Leader posts at ETH (2005) and EMBL (2007), Berger joined Bristol as Full Professor of Biochemistry (2014) with a joint appointment in Chemistry (2019). He is Founding Director of the Max Planck Centre for Minimal Biology in Bristol, Director of the BBSRC/EPSRC research center for synthetic biology BrisSynBio and Co-director of the Bristol Biodesign Institute BBI.

Imre Berger holds international patents for DNA and protein technologies, co-founded three biotech companies, and received numerous distinctions, notably the Swiss Technology Award, the W.A. DeVigier Foundation Award, and a Wellcome Trust Senior Investigator Award for his innovative research. Since 2019, he is an Investigator of the European Research Council (ERC).

Prof. Berger has participated in leading roles in numerous European Commission (EC) projects, including the pan-European structural biology infrastructure INSTRUCT. He has been Coordinator of the EC FP7 HEALTH ComplexINC project enhancing production tools for complex biologics in academic and industrial R&D (2011-2016) and is partner in the EPSRC funded Innovative Future Vaccine Manufacturing Research Hub.

Sina Bavari, PhD

CSO, Edge BioInnovation Consulting and Management; former CSO, Scientific Director US Army Medical Research Institute of Infectious Diseases (USAMRIID)

Dr. Sina Bavari is the co-founder of Healion Bio. He is one of the lead (non-gov) scientific adviser to the World Health Organization on SARSCoV-2. He has spent over 30 years developing rapid response diagnostics, prophylaxis, therapeutics, and vaccines for some of the world’s deadliest infectious diseases. Prior to co-founding Healion Bio, Dr. Bavari founded Edge BioInnovation Consulting and Mgt. and was the Chief Scientific Officer and Scientific Director at USAMRIID (US Army Research Institute of Infectious Diseases), where he spent over twenty years leading the discovery and development of vaccines, therapeutics, and diagnostics or diseases such as SARS and MERS CoVs, Ebola, Marburg, Zika, Smallpox, Sudan, Nipah, alpha viruses, Anthrax and many others. He has worked extensively with the FDA to successfully develop clinically proven countermeasures for many so-called envelope viruses like SARS-CoV-2. Dr. Bavari has contributed to ~20 drug development candidates such as Remdesivir, 30 patents, and many IND filings. He has trained over 70 scientists and managed over 500 scientists and supporting staff. His work has resulted in over 350 publications in many of the leading scientific journals including Nature, Nature Medicine, Cell, Cell Hosts, New England Journal of Medicine and many others. He has degrees from USC, and the University of Nebraska where he received his PhD in Immunotoxicology and Pharmaceutical Science.

Therapeutics Pipeline for COVID-19

Get the latest updates, interviews and receive special offers

Pre-register Today!

Ralph Rogers, MD

Assistant Professor of Medicine, Clinician Educator, Infectious Diseases, Warren Alpert Medical School of Brown University

Ralph Rogers, MD is an infectious disease specialist at the Lifespan Cancer Institute. He earned his medical degree from The Warren Alpert Medical School of Brown University where he also completed his residency and fellowship in infectious diseases. Dr. Rogers is Assistant Professor of Medicine, Clinician Educator Division of Infectious Diseases Warren Alpert Medical School of Brown University. He is a member of the Infectious Diseases Society of America (IDSA), the American Society for Microbiology (ASM) and the American Society of Transplantation (AST).

John Sninsky, PhD

Consultant, Translational Sciences

John J. Sninsky, PhD is a translational medicine consultant with deep understanding of diagnostics and diagnostics paired with medicine intervention. John has served in senior management positions in small and large CLIA service laboratories and in vitro diagnostic kit companies including Cetus, Roche Molecular Systems, Celera, Quest and CareDx. He was a member of the pioneering Cetus team that developed and optimized PCR technology for research and diagnostic use; specifically, the virology team developed the HIV, HTLV, HPV, HCV and HBV PCR assays. John put in place a surveillance initiative for viral variants and presented at the first FDA PMA advisory meeting for HIV PCR approval.

Timothy J. O’Leary, MD, PhD

Adjunct Professor, Pathology, University of Maryland School of Medicine; Former Chief Research and Development Officer, Veterans Affairs

Timothy O’Leary, MD, is Adjunct Professor of Pathology at the University of Maryland and served as Chief Research and Development Officer (CRADO) of the Department of Veterans Affairs from 2013-2015. He holds a doctorate in physical chemistry from Stanford University and a medical degree from the University of Michigan.

He is certified in anatomic pathology by the American Board of Pathology and in molecular genetic pathology by the American Board of Pathology and the American Board of Medical Genetics. Prior to his VA service, O’Leary chaired the Department of Cellular Pathology and Genetics at the Armed Forces Institute of Pathology for more than 15 years. He joined VA in 2004 and served as Director of Biomedical Laboratory Research and Development, Director of Clinical Sciences Research and Development, and Deputy CRADO prior to his appointment as CRADO. O’Leary also served as a reserve member of the Public Health Service Commissioned Corps from 1979 to 2010, serving two tours on active duty. His research interests include genomics, proteomics, and ultrasensitive detection of biological toxins. He has served on numerous federal panels and advisory committees, including the Health and Human Services Clinical Laboratory Improvement Advisory Committee and the Food and Drug Administration Hematology and Devices Panel. O’Leary, the holder of four patents, has authored or co-authored more than 190 journal articles and numerous book chapters and technical reports. He is a past president of the Association for Molecular Pathology and served as editor-in-chief for the Journal of Molecular Diagnostics.