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“We hope to have a vaccine ready for testing in about two years,” Margaret Heckler, the secretary of Health and Human Services, said in a news conference announcing the discovery of the cause of the then-new disease, AIDS. She continued: “Yet another terrible disease is about to yield to patience, persistence and outright genius.” This was 1984. It’s now 36 years later and we still have no vaccine to prevent HIV infection.
In early March of this year, when asked about the timeline for the development of a vaccine against SARS-CoV2 (the virus that causes Covid-19), President Trump said, “I don’t know what the time will be. I’ve heard very quick numbers, that of months. And I’ve heard pretty much a year would be an outside number. So, I think that’s not a bad range. But if you’re talking about three to four months in a couple of cases, a year in other cases.” Experts in the room, including Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, tried to temper expectations, but also offered a timeline of 12–18 months for the development of a vaccine. Dr. Fauci has been director of NIAID since 1984, the year Secretary Heckler made her prediction. Will Dr. Fauci’s optimism be prescient or premature?
Most experts I spoke to recently, including Dr. John Moore, professor of microbiology and immunology at Cornell-Weill Medical College and Dennis Burton, professor of immunology and microbiology at the Scripps Research Institute, and both veterans of the search for an AIDS vaccine, weren’t ready to make prognostications. In fact, it takes a long time to develop a vaccine—timelines denominated in years rather than months. However, should Dr. Fauci’s prediction turn out to be wrong, it won’t be for lack of trying. A new paradigm is emerging for vaccine development in the age of Covid-19, in which many of the steps are truncated or happening simultaneously. There are about 90 vaccine candidates in the pipeline right now for Covid-19.
Early bets are being made on a few vaccines, which even in the absence of evidence of their safety and efficacy are being scaled up, with millions of doses being manufactured now or in the planning stages with support from the federal government’s Biomedical Advanced Research and Development Authority (whose director, Rick Bright, was purged in mid-April for criticizing the White House’s obsession with hydroxychloroquine) and private companies like Johnson & Johnson and Sanofi. This may turn out to be a multibillion-dollar fumble, but the logic is that we do not have time to waste on the months and months it will take to scale up production of these vaccines, should they actually turn out to work.
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However, the urgency with which the development of a vaccine is being approached cannot obviate the scientific obstacles to finding one. First, remember this is a new pathogen: SARS-COV2 emerged only a few months ago and scientists are still learning about how it works, and importantly, how our bodies’ immune systems respond to it. We still don’t know what the correlates of protection are for SARS-COV2—meaning the “quantifiable immune parameters that determine the attainment of protection against a given pathogen,” that is, what part of the immune response, and in what magnitude, keeps you free from infection if you encounter the virus.
As I mentioned in my article about testing two weeks ago, there are some hospitalized patients with Covid-19 who only develop low levels of antibodies to SARS-COV2, with about 5 percent showing no antibody response at all. A new French study suggests that antibody responses in those with mild or asymptomatic infection may be even more difficult to detect due to low levels of antibody as well. In any case, do antibodies to SARS-COV2 confer protection—and how long does this protection last? Tests of an inactivated SARS-COV2 vaccine in rhesus macaques shows promise in generating neutralizing antibodies and protection against infection, but how will this play out in the human host? Might other parts of the immune system be crucial in protecting against this new coronavirus? We simply do not know the answers to these questions right now.
And there are potential pitfalls. Some vaccines can cause immune system malfunctions, in which vaccines can set up an immune response that, instead of protecting you from infection, makes the disease worse if you catch the virus. We’ve seen this in vaccine development for diseases like dengue, respiratory syncytial virus (RSV), and severe acute respiratory syndrome (SARS) and so careful testing of vaccine products looking out for these paradoxical effects is going to be important as we move forward. Some of the technologies on which these vaccines are based are also untried, particularly the RNA-based vaccines that are at the center of discussion right now and had President Trump trying to secure rights to a German mRNA (the m here stands for “messenger”) vaccine for exclusive US use.
There are lots of hurdles in the development of a SARS-COV2 vaccine, both scientific and practical, and we haven’t even begun to discuss the complicated ethical issues involved in clinical trials and determining how we’ll deal with who gets access to an approved successful vaccine, when billions may need it. However, one thing is clear: We do desperately need a vaccine. Vaccine development, like public health more generally, is a matter of the common good: Vaccines often don’t make profits, and public health doesn’t make people rich, so it’s up to us to invest as a society to develop them and to protect the public health. In the midst of pandemics, no one needs convincing of the urgency of these tasks. It will be after the social distancing is over, when we’ve gone back to our lives, that we might forget that investing in vaccine development and public health is still urgent—for the diseases that are just around the corner, or those which will never leave us alone, unbothered, unless we vanquish them, once and for all.