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Writer's pictureP.K. Peterson

Race for a Vaccine Against COVID-19: Where’s the Smart Money?

“The world has now witnessed the compression of 6 years of work into 6 months. Can the vaccine multiverse do it again, leading to a reality of a safe, efficacious Covid-19 vaccine for the most vulnerable in the next 6?” (NEJM editorial, July 14, 2020)

- Penny Heaton, CEO, Bill & Melinda Gates Medical Research Institute

“Without equity, pandemic battles will fail. Viruses will simply recirculate, and perhaps undergo mutations or changes that render vaccines useless, passing through the unprotected populations of the planet.”

- Laurie Garrett, American Science Journalist and Author

More than 150 vaccines are being developed against SARS-CoV-2 by research teams in companies and universities around the world. On May 15, President Trump announced “Operation Warp Speed” designating 10 billion dollars for research to develop a vaccine against SARS-COV-2 by the beginning of 2021. By June 3, his administration, which includes the National Institutes of Health, had selected five coronavirus vaccine research teams for funding. The race was on.

On July 14, the New England Journal of Medicine published “An mRNA vaccine against SARS-CoV-2—Preliminary Report,” which provided the results of a Phase I clinical trial of one of these front runner vaccine candidates. Now seems like a good time for a Germ Gem post to review not only the basics of how vaccines work but also the positions of the top five horses competing in this momentous life-saving race.

Vaccine basics. Vaccination trains cells in the body’s immune system to recognize (remember) and respond to infectious agents or to their molecules (called antigens)—in the case of COVID-19, we are talking about the coronavirus SARS-CoV-2, its proteins (peptides), such as, the spike (S) protein that it uses to enter cells via ACE2 receptors, and its nucleic acid (mRNA). For use in a vaccine, a virus is attenuated or inactivated, which means it’s unable to cause disease but is still capable of triggering an immune response.

Development of immunity to a pathogen involves what is called the adaptive immune system (a coordinated network of antigen-presenting cells, B and T lymphocytes, cell mediators, such as cytokines, and antibodies). Almost all effective vaccines induce an antibody and a T lymphocyte response. (To me, this phenomenon is nothing short of miraculous.)

There is a long track record of safety and efficacy of vaccines that make use of attenuated microbes and microbial antigens to elicit immunity. In fact, currently more than 85 vaccines are licensed by the U.S. Food and Drug Administration (FDA) for use in humans. But, to date no nucleic acid (DNA- or RNA-based) vaccines are licensed for use. (mRNA vaccines take a novel approach that is faster as it bypasses the more laborious tasks of inactivating viruses or isolating peptides.)

Top five vaccine candidates. The Trump Administration has “bet” on (funded) these five contenders.


Moderna Therapeutics: As reported in the New England Journal of Medicine article mentioned above, this Massachusetts-based biotechnology firm has completed a Phase I trial of its mRNA vaccine. (The goal of Phase I trials is mainly to assess safety.) The results of its first trial were considered successful; that is, the vaccine was sufficiently safe plus it elicited immune responses in all 45 adult participants. The company has moved onto Phase II clinical trials.

Oxford University/AstraZeneca: In April, Sarah Gilbert and her colleagues at Oxford’s Jenner Institute initiated a human phase I trial on 1,100 people of a novel vaccine, the technical name of which is ChAdOx1 nCoV-19, as it is made from a virus called ChAdOx, which is a weakened and non-replicating version of an adenovirus that causes the common cold in chimpanzees. The vaccine has been engineered to express the SARS-CoV-2 spike protein. On July 20, it was announced that all of the vaccinees in the trial developed neutralizing antibodies and T lymphocyte responses, and no serious side effects were observed.

The Oxford group teamed up with the British pharmaceutical company AstraZeneca, which agreed to sell the vaccine on a not-for-profit basis during the COVID-19 crisis and lined up deals with multiple manufacturers to produce more than 2 billion doses. Subsequently, they leap-frogged ahead of all other vaccine contenders and have begun planning Phase II/III trials in multiple countries involving people of a wide age range. The UK has already ordered 100 million doses of the vaccine.

Merck: In May, Merck, one of the largest and most successful vaccine makers in the world, announced that it is developing two different vaccines for COVID-19. One vaccine candidate is under development by Themis, a Viennese company spun out of the Institut Pasteur in Paris (recently acquired by Merck). The vaccine uses a weakened measles virus to slip parts of SARS-CoV-2 into white blood cells, generating an immune response. Researchers will carry out human studies in France. For the second vaccine candidate, Merck is partnering with the nonprofit IAVI on the development of a vaccine related to Merck’s existing Ebola vaccine. Their SARS-CoV-2 vaccine could enter trials later this year.

Pfizer Inc./BioNTech: On July 13, the U.S. FDA granted Fast Track status to two investigational vaccine candidates being developed by the American drug giant Pfizer and its German biotech partner BioNTech. Both vaccine candidates are mRNA-based products. (Fast Track designation was based on early data released from ongoing Phase I/II studies in a program called “Project Lightspeed.”) Subject to regulatory approval, the companies are expecting to start a Phase II/III trial by the end of July and anticipate enrolling up to 30,000 subjects in the trial. And if the ongoing studies are successful, and a vaccine candidate receives regulatory approval, the companies currently expect to manufacture up to 100 million doses by the end of 2020 and potentially more than 1.2 billion doses by the end of 2021.

Johnson & Johnson: Johnson & Johnson is one of the world’s biggest pharmaceutical companies, but it has been a relatively small player in the vaccine market. (The company’s Ebola vaccine received approval from the European Commission earlier in July 2020.) Nonetheless, the U.S. government provided the company $456 million from the Trump Administration’s Operation Warp Speed program to ramp up development of a vaccine they’ve been working on in collaboration with Janssen Pharmaceuticals, a division of Johnson & Johnson in Belgium. Their approach to a potential vaccine is built upon an inactivated common cold virus (Adenovirus 26) that’s non- replicating but encodes for peptides of SARS-CoV-2. This helps create a vaccine with a known safety profile. Based on animal studies, they anticipate beginning clinical trials by September.

While the vaccines under development by the big five Western companies listed above all look like good bets, vaccines are also under development in other countries, most importantly in China.

Don’t count the Chinese out of the race. On July 7, World News published an article: “At war time speed, China leads COVID-19 vaccine race” summarizing China’s commitment to develop a vaccine against COVID-19. Challenging the West’s traditional dominance of the vaccine industry, China is behind eight of the 19 vaccines in human trials. Unlike most Western vaccine products, China’s vaccine technology is focused mainly on tried-and-proved inactivated vaccine technology, such as that used for influenza and measles virus. One vaccine product produced by the Chinese company Sinovac is set to begin Phase III trials later this month.

What are some of the major roadblocks ahead? In addition to surmounting the staggering challenges of developing safe and effective vaccines to protect billions of people worldwide, including those living in poverty-stricken communities, many other issues need to be resolved. Tough questions include:


1) Who gets vaccinated first? The elderly are the biggest risk group for acquiring fatal COVID-19 but they are also the least likely to develop a robust immune response to a vaccine. So starting with younger people may make more sense to help build herd (community) immunity faster. Health care workers are also at increased risk of COVID-19, and their services are critical in combatting the pandemic. Thus, it seems highly likely that health care workers will be the first in line for immunization.


2) How effective does a vaccine need to be before it is used? All of us would like to see a COVID-19 vaccine that is effective as the measles or polio vaccines, which protect close to everyone. That may not be initially possible, however. Perhaps 50% coverage, the current efficacy of the flu vaccine, would be effective in stemming the tide of the pandemic.


3) Could the blistering speed of vaccine development work against the acceptance of vaccines? This is an especially worrisome consideration if safety becomes a problem. Anti-vaxxers are already geared up to stifle COVID-19 vaccine development, and they would pounce on any hint of lack of safety. And, even without the anti-vaxxers, a growing number of polls find many Americans saying they would not get a vaccine because of mistrust in the FDA and the Trump administration. So, safety has to be the primary concern of any vaccine that is developed.


4) Could SARS-CoV-2 mutate and make one or more vaccines ineffective? So far, no major genetic changes in the virus have been detected. We are, however, still in the early stages of the pandemic and cannot rule out a mutation that would make a vaccine useless.


5) What if the COVID-19 pandemic peters out naturally, so an insufficient number of people are available to vaccinate? I think this is a problem we all would welcome.

So where is the smart money? Like all horse races, odds are in favor of one or more of the above vaccines making it to the market by early 2021. But, don’t forget there are a number of dark horses (at least another 90 vaccine candidates are in early stages of development). Of course, the biggest winner of this race will be all of us. Our fate is riding on it.

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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.

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