Coronavirus Vaccines

The Medical Letter’s online table of Treatments Considered for COVID-19 now includes a section on vaccines, neatly arranged by mechanism of action: adenovirus-vectored, mRNA, adjuvanted recombinant nanoparticle, and inactivated vaccines. Our list is incomplete, of course, because the number of vaccines now in clinical trials around the world is approaching 50, but we have included those with significant clinical trial results.

Last week I watched Dr Howard Bauchner, the Editor-in-Chief of JAMA, interview Dr Paul Offit, a dazzling pediatrician/vaccinologist from the University of Pennsylvania. I would urge anyone with an interest in this subject (which I guess means almost everyone) to watch their 40-minute discussion. I watched a second time and took notes to share on this blog, but in no way can my notes do justice to the content. In the interest of readability, I have omitted repeated attributions here. Almost all of the content below reflects Paul Offit’s answers to Howard Bauchner’s questions.

The interview appeared online two days after the FDA announced an Emergency Use Authorization for convalescent plasma that provoked many negative comments in the medical community because no randomized controlled trial had established its efficacy in treating COVID-19. The apparent bullying of the FDA, which was reminiscent of the agency’s EUA for hydroxychloroquine, was disturbing in its own right, but more importantly raised the spectre of premature approval of an inadequately tested vaccine that could do great harm in a vaccine-skittish country. Perhaps the vaccine manufacturers could save the day by refusing to release their products until adequate clinical trial results became available, but that would depend on their willingness to forego a quick profit and the wording of their contracts with the federal government.

Does it matter which vaccines emerge as the winners in this race? Results of the phase 1 trials of the messenger RNA and adenovirus vector vaccines suggest that 2 doses will be needed to achieve effective antibody levels. If we are to vaccinate 120,000,000 people, we will need 240,000,000 doses. A live attenuated vaccine may only require a single dose. All of these vaccines produce fewer antibodies in the elderly; an adjuvanted vaccine might be the best bet for that population. The Russian vaccine appears to be a combination of 2 adenovirus vector vaccines, one with adeno 20 and the other with adeno 5. Since these vectors don’t replicate, you have to give a lot of virus, which could cause reactions. Many of these are novel vaccines, and their safety must be well established. Hopefully, a vaccine that produces no serious safety signals in 20,000 recipients will be safe in 20,000,000 as well.

Could herd immunity come to our rescue in the foreseeable future? Herd immunity will not eliminate this virus. It has never eliminated any virus except smallpox. Measles virus, varicella and poliovirus still exist, and if we stop vaccinating, they will rise again. The best we can do with SARS-CoV-2 is to stop its spread, but that would probably require a 75%-effective vaccine given to two-thirds of the population – a tall order.

The reinfection reported recently in a young man from Hong Kong appears to be a true bill; the second virus was different from the first. He had mild symptoms in his first infection and none in the second, but the second infection produced a substantial spike in the antibody levels still present from the first infection. From the patient’s perspective, that is ideal. But will he transmit the virus from his reinfection to others? We don’t know yet.

And there is more, much more. Dr Offit talks fast. And smart. By all means, listen to the real thing.

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