Science prevailed in FDA advisers rejecting COVID-19 boosters for everyone

The recent votes by the FDA Vaccines and Related Biological Products Advisory Committee (VRBAC) not to issue a blanket approval of booster doses of Pfizer’s COVID-19 vaccine for those above the age of 16 — but to issue a narrower one focused on those above the age of 65 or at high risk of severe COVID-19 — surprised many. However, if one parsed the data, understands the immune system and reflected on the question of what COVID-19 vaccines were designed to accomplish the decision was not surprising, but correct.

The most important aspect of COVID-19 vaccines is their ability to prevent severe disease, hospitalization and death. That is what they were designed to do, and they are doing it brilliantly for most people with a combination of antibodies and T-cells. Indeed, the initial FDA authorizations of the COVID-19 vaccine were based on the ability of the vaccines to stop disease (i.e., symptoms).

It is critical to realize that vaccines are not bug zappers; they are not forcefields. That breakthrough (a term itself falsely connotes vaccine failure) infections are mild is a vaccine success, even as they may increase in frequency. Breakthroughs were expected. We must remember it is disease, not clinically irrelevant infections we are targeting and that is done with first and second doses — not a third. That these breakthrough infections are often associated, not with virus in lung, but in the nose — a location where antibody protection with current vaccines may be lacking — are associated with a rapid decline in viral load and often do not yield cultivatable virus attests to their relatively mild nature.

COVID-19 is an endemic respiratory virus, it cannot be eliminated or eradicated. As such, there is marginal utility in the general healthy population getting booster vaccinations at 6-month interval because the protection they have against severe disease is intact. Granted, there is little harm in third doses (although there are concerns about myocarditis risks in younger populations). But, is chasing mild infections in the fully vaccinated an important task? Boosting this group would not change the trajectory of the pandemic in the U.S. or the world. Improved second generation vaccines, perhaps those that induce immunity in the nasal passages, may take on this task but I do not think boosting the low-risk population is justified with current vaccines.

Some point to diminished antibody levels to argue the case for boosters. However, it is well established that antibody levels fall over time and then spring back up post-exposure (to the virus or the vaccine). That is how the immune system works — it is anamnestic. It “remembers” after the primary response and mounts a heightened response that staves off severe illness using both T-cells and antibodies in the secondary response. We fully expect antibodies to fall as time from exposure to vaccine or infection increases and we fully expect them to rise upon re-exposure. This isn’t vaccine failure; it’s just how the immune system works. That infections in the vaccinated are generally mild is evidence of this process working. Mild or clinically silent infections are not major worries. Hospitalized COVID-19 patients are, for the most part, not vaccinated.

When the Centers for Disease Control and Prevention (CDC) recommended a modification of the primary immunization series for the immunocompromised — which is distinct from a booster — it did so based on clinical evidence that amongst the relatively rare COVID-19 hospitalizations of vaccinated individuals, the immunocompromised were overrepresented ( about 45 percent in a non-peer reviewed paper). Additionally, a study in solid organ transplant patients revealed not only did they, as expected based on experience with other vaccines, fail to mount a robust (or sometimes any) antibody response but had a 485 times increased chance of COVID-19 hospitalization versus someone without a transplant. That type of clinical evidence was then integrated with data on third doses of mRNA vaccines increasing antibody levels in these populations. 

Clinical data on the occurrence of severe infection occurring in older Pfizer vaccine recipients does exist, and was presented, showing that an amount of diminution of protection against severe disease is apparent. Some of that data was derived from Israel and may not be directly extrapolatable to the U.S. as Israel uses a lower threshold to label a COVID-19 case severe but, nonetheless, it still has significant relevancy. That older age groups may have waning protection is not surprising. With many other vaccines, older age groups have overall less robust responses to vaccines and are at a higher risk for severe disease generally.

When President Biden made a general booster recommendation to the public in August, none of the type of nuanced clinical data presented today was thoroughly discussed or made available to support his statement. This was why it was met with disapproval by many members of the infectious disease community. Now that FDA’s vaccine advisory committee has made a clinical data-based recommendation that the FDA will likely ratify it will next fall to the CDC’s Advisory Committee on Immunization Practices (ACIP) to debate (next week) whether to make a recommendation for the commencement of a booster program, delineate the risk groups below 65 years, and determine the optimal timing of the vaccine.

The lesson of the COVID-19 booster debate is that science prevailed and an evidence-based discussion, anchored to clinical outcomes, motivated the vaccine advisory committee votes.

Amesh Adalja, M.D., is an infectious disease physician and a senior scholar at the Johns Hopkins Center for Health Security. Follow him on Twitter: @AmeshAA