The emergency use authorizations of mRNA vaccines by Pfizer/BioNTech and Moderna and the likely gradual rollout of multiple others is our collective best hope for curtailing the Covid-19 pandemic.
The speed at which these vaccines has been developed is remarkable, both in absolute terms and compared to the multiyear time frame it normally takes to create and approve new vaccines. Great credit is due to the pharmaceutical industry and the university and government scientists who have worked directly and diligently on Covid-19 vaccine programs in the U.S., Europe, and elsewhere. They deserve accolades for their skillful hard work.
But the Covid-19 vaccines did not come from nowhere. Decades of research by tens of thousands of scientists worldwide put in place the essential knowledge and methods that underpinned their rapid development.
In the U.S. alone, the National Institutes of Health provides approximately $4 billion dollars a year to immunology and vaccine research programs, with further substantial support from private funders such as the Bill and Melinda Gates Foundation. These multiyear, multimillion dollar investments in basic science provided the foundation from which the new vaccines rapidly emerged.
SARS-CoV-2, the virus that causes Covid-19, is a coronavirus. Research over the past two decades on the earlier severe acute respiratory syndrome (SARS) virus and its cousin, the virus that causes Middle East respiratory syndrome (MERS), taught virologists and vaccine designers a great deal about coronaviruses, their vulnerabilities, and how they might best be exploited.
A cadre of researchers with critically important knowledge of this virus family was able to guide the scientific community in how to respond to the Covid-19 pandemic.
Many of the technologies now used widely for vaccine design are rooted in longstanding programs to fight HIV and influenza. For various reasons that relate to the properties of the viruses themselves, those pathogens are much more difficult to vaccinate against than SARS-CoV-2, but the accrued knowledge of how to counter them has been invaluable.
The recently approved monoclonal antibody Covid-19 therapies from Eli Lilly and Regeneron also benefitted greatly from the techniques used to identify and produce similar antibodies for HIV clinical trials and also led to the antibody cocktails that were used to treat people infected with Ebola virus.
When Chinese scientists published the SARS-CoV-2 genome sequence on the internet on Jan. 10, 2020, multiple vaccine programs were started within days because existing vaccine design methods could be repurposed.
All of the leading vaccines are based on the SARS-CoV-2 spike protein, the entity on the virus surface that drives infection of human cells. Humans infected with SAR-CoV-2 raise antibodies against the spike-protein that prevent further infection by neutralizing the virus.
The various vaccines present the spike protein to the immune systems in different way but with a common purpose: triggering the immune system to produce antibodies that neutralize the virus as soon as it is encountered, thereby preventing or limiting the infection.
Decades of work, first on the corresponding HIV spike protein and then its counterparts from other viruses, including SARS, MERS, and seasonal coronaviruses, showed how best to design and produce the SARS-CoV-2 version. Sophisticated methods to image the spike proteins via recent advances in electron microscopy allowed researchers and vaccine makers rapidly to study what they were making, gaining assurances that they were on the right track.
The Pfizer/BioNTech and Moderna/NIH vaccines deliver the spike protein in the form of mRNA. This technology emerged during the past decade from university laboratories working on HIV and influenza vaccines, which then triggered Zika, Ebola, and coronavirus vaccine programs at the NIH and in the pharmaceutical industry. The Moderna mRNA vaccine, in particular, was made as a collaboration with the NIH’s Vaccine Research Center, funded by U.S. taxpayers since 1997 to create vaccines against deadly viruses and other human diseases. A method developed by Janssen, a pharmaceutical company, to present spike proteins to the immune system also emerged from an HIV vaccine program at Harvard University. AstraZeneca’s version of the adenovirus delivery system has a similar history. Decades of work on the corresponding HIV and influenza proteins, as well as coronavirus proteins, underpin the Novavax SARS-CoV-2 spike protein vaccine design. DNA vaccines are also in clinical trials, another method derived from research on HIV and other viral pathogens.
Some of the vaccine trials have been conducted by the pharmaceutical industry. However, an extensive network of trial sites funded by the NIH for HIV vaccine clinical research is playing a key role. Fundamental immunology research programs in U.S. universities developed the techniques to study how humans respond both to viruses like SARS-CoV-2 and the vaccines that counter them. Existing methods only needed to be adjusted for the new virus. Comparisons to immune responses in infected people will be essential for understanding how the Covid-19 vaccines perform in the longer term.
U.S. taxpayers are spending approximately $18 billion dollars on the production and distribution of Covid-19 vaccines via Operation Warp Speed. That effort would not have been possible without the prior expenditure of much smaller sums on basic immunology and vaccinology research. As two researchers who have spent many years working on viral pathogens, we believe that this funding has been very well-spent.
Funding scientific research is buying an insurance policy for a better future. The benefits are not always apparent, and sometimes become visible only over many years. 2020 is a case in point: The nation’s existing research infrastructure laid the groundwork for Covid-19 vaccines to be designed within weeks of the emergence of a deadly virus and produced within months.
We cannot know when the next global health crisis will hit, but we do know that continuing to support medical science is essential for a rapid and effective response when it does.
John P. Moore is a professor of microbiology and immunology at Weill Cornell Medicine in New York City. Ian A. Wilson is professor and chair of the Department of Integrative Structural and Computational Biology at the Scripps Research Institute in La Jolla, Calif.
As Issac Newton said in 1675, “If I have seen further it is by standing on the shoulders of Giants.” Still true today, and all good scientists will quickly acknowledge this.
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