In a March 13 interview with CBS, Albert Bourla, Pfizer’s CEO, said his company intended to apply to the Food and Drug Administration for authorization of a fourth mRNA vaccine dose and implied that this was something all adults needed. Two days later, it did just that — but only for adults over 65.
That same day, Stephen Hoge, Moderna’s president, took a different perspective: that a fourth dose of his company’s mRNA vaccine wasn’t required for all adults but could benefit older and immunocompromised Americans. Two days later, Moderna announced it was requesting FDA authorization of a fourth vaccine dose for everyone aged 18 or over.
So over a mere four-day period, the two mRNA vaccine companies made internally inconsistent and seemingly arbitrary statements, and then took different actions.
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Is competition between the two companies for market share now a factor in their decisions? Are they seeing the science differently? And when company executives are, in effect, saying “our vaccines are no longer doing very well, so you need more of them,” isn’t there a risk of playing into the anti-vaccine narrative that vaccines don’t work?
Adding further confusion, Moderna had announced only a week earlier that it was developing a Delta-plus-Omicron bivalent vaccine (a bivalent vaccine works by stimulating an immune response against two different antigens, in this case two different variants) for possible rollout later this year. That idea was greeted with mixed opinions. Would updating the composition of the current vaccine make a difference, and would a bivalent vaccine actually be useful?
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Whatever is behind these events, they risk further confusing the public. The two of us have already received requests from perfectly healthy, vaccine-enthusiastic friends about whether, where, and how they can obtain their fourth vaccine doses. Others have asked us — and our colleagues — if they should delay being boosted again until Moderna’s “better vaccine” was available later in the year.
Covid-19 vaccine policy should never be made by company executives via media outlets and press releases. At the very least, there is the perception of a lack of objectivity — it is in the best financial interest of any company to sell more of its product. National vaccine policy is, and should remain, a deliberate, data-driven process led by the federal government. Federal advisory committees — the Vaccines and Related Biological Products Advisory Committee (VRBPAC) for the Food and Drug Administration, the Advisory Committee on Immunization Practices for the Centers for Disease Control and Prevention, and the National Vaccine Program Office for Department of Health and Human Services — play essential roles by evaluating data objectively and assessing what is best for public health.
In fact, the VRBPAC announced on Monday that it would meet on April 6 to consider vaccine boosters for Covid-19.
Scientific and public health advisers, as well as vaccine companies’ scientists, have long provided substantial public input to these independent advisory committees.
All of this should be obvious. Yet what is now happening recapitulates some of the events of last summer and fall, when company executives drove the narrative that a third mRNA vaccine dose was essential for all Americans, creating anxiety within the ranks of the vaccine-embracing public and setting up a scenario in which the Biden administration’s senior health experts overruled narrower recommendations for boosters made by the FDA and CDC advisory committees. None of this reflected optimal decision-taking.
U.S. health policy can — and should — be better made.
What does the science say about the need for a fourth dose? What will the future trajectory of the pandemic look like? What is vaccination supposed to accomplish? Does everyone benefit from additional vaccine doses? And why is Pfizer asking for approval for a fourth dose only for individuals over age 65, but Moderna is asking approval for all adults?
To answer these questions, the federal government first needs to clearly establish and communicate the goals of its national Covid-19 vaccination program. Second, it needs reliable data to understand the extent to which both vaccine and infection-derived immunity are waning over time, and what this means for protection against severe disease, hospitalization, and death. This information should be collected for the young and old as well as for healthy, ill, and immunocompromised individuals. And vaccine policy cannot be evaluated in a vacuum: Vaccines are not the only solution to the pandemic; excellent therapies are now available are an important complementary tool.
All of the vaccines authorized for use in the United States against Covid-19 do an excellent job at keeping people out of hospitals and alive. Even just two doses of the mRNA vaccines are very effective, especially when combined with infection-derived immunity (now present in a substantial number of people due to the Omicron wave). A third dose has brought some, but only modest, additional benefit for this important measure of vaccine efficacy.
A correspondence from Israel that the New England Journal of Medicine published on March 16 questions whether a fourth Pfizer or Moderna dose is useful. The authors stated that “a fourth vaccination of healthy young health care workers may have only marginal benefits.” The reasons are that immunological memory and the full complement of our immune systems’ tools develop and mature in the weeks and months after the initial two-dose vaccination series. Those protective mechanisms don’t wane over time in the same way that the initial antibody titers do; in fact they actually become stronger.
Where problems have arisen relates to mild infections, first during the latter months of 2021 when antibody-based immunity to the mRNA vaccines began to decrease (more so for the Pfizer vaccine than Moderna’s); and then in the past three months during the Omicron surge. The combination of reduced antibody titers and the more antibody-resistant variant drove a large number of asymptomatic and mild infections in vaccinated people. A third dose provided some additional protection. However, between 90% and 95% of the Americans who died of Covid-19 during the Omicron surge were unvaccinated. Very few vaccinated people entered the ICU and died, and those who did were in very high-risk groups who weren’t able to access effective antiviral drugs in time.
Opinions can legitimately differ about how much emphasis we should place on preventing mild infections in otherwise healthy people. On the one hand, the country never worried much about preventing mild, cold-like symptoms in the pre-pandemic era. Of course it would be desirable to prevent even mild infections, which may cause absences from work and risk onward transmission — perhaps to a more vulnerable relative. But that desire must be tempered by the reality of how vaccines and respiratory viruses work.
A fourth mRNA vaccine dose for the average, healthy American might reduce the incidence of mild infections for a few weeks to months, but it would have minimal additional impact on preventing serious disease and death.
So what do we as a nation want and need? How should we use resources that may become increasingly limited? As we said earlier, it’s essential to rely on objective experts and not corporate executives for the best answers.
Where there is likely to be universal agreement is the need to protect members of society who are most at risk from complications of Covid-19. Immunocompromised people require additional vaccine doses, and in many cases other tools such as prophylactic monoclonal antibody therapies, to prevent Covid-19. Americans over age 65 and those in poor health are other groups in which additional vaccine protection would be beneficial. But there is a world of difference between a 75-year-old man with diabetes and a healthy college athlete in her 20s. The FDA’s advisory committee recognized the distinction last year when it was asked to weigh in on a third dose, yet the prevailing social dynamic drove the Biden administration to recommend boosters for every adult.
What happened last year should not be repeated in the coming months.
In the longer term, will the FDA receive regular requests to authorize additional boosters? Will a Covid-19 vaccine become similar to its influenza counterpart: an annual routine? Much depends on the future of the pandemic. Will new surges of infection happen later this year and, if so, triggered by what variant? Or will the Omicron wave be the pandemic’s last hurrah?
While it is important to plan in advance, it seems unlikely that Omicron-specific boosters will be needed in the near future, as the standard vaccine is likely to be as effective. There’s no need to decide right now what should be done in the fall. We believe it would be most prudent to see what happens over the summer while both the circulation of the virus and the state of our individual and collective immune responses to it are carefully monitored.
Given the expertise available, a decision grounded in science and facts is likely to be the right decision.
John P. Moore is a professor of microbiology and immunology at Weill Cornell Medicine in New York City. Luciana L. Borio is an infectious disease physician, a senior fellow for global health at the Council on Foreign Relations, and former director for medical and biodefense preparedness policy at the National Security Council. The authors have no links to any companies producing or evaluating any of the vaccines mentioned in this article, and declare no conflicts of interest.
