A quartet of infectious disease, vaccinology, and virology experts share thoughts on the FDA's newest emergency authorization for COVID-19 mRNA vaccines.
On Thursday, the US Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) to Pfizer-BioNTech and Moderna for the use of third "booster" doses of the companies' COVID-19 mRNA vaccines in severely immunocompromised patients in the US.
The decision preceded guidance from the CDC Advisory Committee on Immunization Practice (ACIP) Friday afternoon on the specifics of immunocompromised patient immunization strategies, providing a streamlined federal pathway toward ensuring patients of solid organ transplants or receiving chemotherapy—among other immunosuppressing modes of care—are optimally protected from COVID-19 risk.
Through the week, Contagion spoke to infectious disease, virology, and vaccinology experts on the merits of a booster vaccine dose EUA. Here are some of their thoughts, following the FDA decision.
Peter Hotez, MD, PhD, Professor, Departments of Pediatrics, Molecular Virology & Microbiology, Health Policy Scholar, Baylor College of Medicine: I think the need for a third immunization—which some people are calling a booster but I think of as almost like a primary immunization series in order to get a full-fledged immune response, in many cases—is not unexpected. Most of our vaccines require more than 2 doses, and some even 4 or 5. I don’t think that’s going to be necessary, but I can envision that a third one will be necessary, at least based on what we’ve seen from measuring virus-neutralizing antibodies—which is not a true correlate of protection, but has a lot going for it in terms of linking it to protective immunity.
In the case of solid organ transplant recipients getting immunosuppressive therapy, there were 2 studies earlier this year from Johns Hopkins and France showing that those who got 2 doses of vaccines, some were non-responders and others responded with very little levels of virus-neutralizing antibodies and benefitted from a third immunization. There was another study that just came out in The New England Journal of Medicine (this week) showing that.
So I think there’s compelling evidence that those on immunosuppressive therapy for solid organ transplants would benefit from a third immunization to get the virus-neutralizing antibodies jacked up, and presumably as well as T- and B-cell responses. In terms of a lack of clarity, the question is what other immunocompromising conditions do we need to look at.
Carlos del Rio, MD, Executive Associate Dean, Emory School of Medicine & Grady Health System: The much-awaited FDA modification of the EUA to allow an additional shot for some immunosuppressed patients I think is welcome. The CDC and ACIP couldn’t do anything recommending it until the EUA has been modified, so the first step was the FDA to modify the EUA, which they have done. They’re talking about severely immunocompromised solid organ transplant recipients, of which about one-third don’t respond after 2 doses but seem to have a response after a third dose of the mRNA vaccines. There’s also other immunocompromised patients, such as those receiving some biologics and other agents.
Now the ACIP is going to try to define what “immunocompromised” means. They’re going to have to set limits and try to define what immunocompromised is.
David Weber, MD, MPH, Associate Chief Medical Officer, UNC Health Care: Certainly, I think it’s the right thing to do. First, we know that for severely immunocompromised patients—organ transplant recipients, those on chemotherapy—we know with 2 doses of vaccine, many mount no antibody response. And for those who mount an antibody response, many of them are suboptimal, meaning substantially below the level you would find in a healthy individual. We also know that this translates into lower vaccine effectiveness with COVID-19 when compared to the 95% protection in the studies for the mRNA vaccines against symptomatic disease, and the very high protection against hospitalizations and deaths.
Second, we know that if you give those individuals a third dose, those who have no antibodies will develop antibodies, and those with low antibodies, many—but not all—will develop substantially higher antibodies that would be similar to what a healthy person will mount after 2 doses.
What we don’t know, of course, is how this will translate into improved vaccine effectiveness, because to my knowledge there actually have not been a large number of people given a third dose that have demonstrated improved effectiveness, though it’s a logical conclusion.
And finally, we know that giving those individuals an additional booster dose is safe. They don’t have untold side effects, at least in the short run. They have similar side effects to one of the first 2 doses.
Donald J. Alcendor, PhD, Assistant Professor of Cancer Biology at Meharry Medical College and Adjunct Associate Professor of Cancer Biology at Vanderbilt University School of Medicine: I think the precedent is precautionary based the potential poor immune responses to the vaccines that you might see in individuals that are immunosuppressed. They are more likely to have breakthrough infections that could lead to hospitalizations and death compared to folks who are not immunosuppressed and had good responses to the vaccines.
The delta variant is the main reason for this change, because the immunosuppressed population is most vulnerable and during the rise of the variant; we’ve seen more breakthrough infections and more pediatric hospitalization than before.
It would be great to have a comprehensive study that examines antibody titers in serum from individuals that are immunocompromised and people that are not to gauge a protective antibody response and one that has waned to an unprotected level. There was a time when evidence suggested that 2 doses would last for years.
We do not want drug companies to dictate when and if we need boosters. We need a comprehensive study that demonstrates that antibody levels are falling below protection levels against the current variant. No one is discussing T-cell responses to the vaccines, which are just as important for protection as antibody levels to the virus.