COVID-19 Experts Weigh in on Heterologous Booster Doses

The FDA and CDC have authorized and recommended 3 different booster doses, to be used in "mix-and-match" strategy among eligible adults. What does this mean for immunity?

The landscape of COVID-19 vaccine boosters has changed swiftly and comprehensively in the last 24 hours. Yesterday, the US Food and Drug Administration (FDA) granted emergency use authorization (EUA) to Moderna’s mRNA-1273 and Johnson & Johnson’s Janssen COVID-19 Vaccine as booster dose-administered COVID-19 vaccines, under specific timelines and for certain patient populations.

The FDA additionally expanded the availability of the already-authorized Pfizer-BioNTech BNT162b2 booster dose, while also approving heterologous “mix and match” booster dosing among eligible adults who already received their primary administration.

Then, this afternoon, the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) voted unanimously to recommend the FDA’s booster dose authorizations for the US. With this step cleared, experts now anticipate COVID-19 booster dose rollout and availability will begin in full.

Earlier this week, Contagion® spoke to a trio of vaccinology and immunology experts on the growing support and federal advisories on heterologous COVID-19 booster doses—a strategy that was more greatly embraced after supporting National Institutes of Health (NIH) trial data was presented last week.

The experts shared perspective on what mix and match booster dosing will mean for the US population—as well as for the 3 emergency-authorized vaccine developers.

Donald Alcendor, PhD, Assistant Professor of Cancer Biology at Meharry Medical College and Adjunct Associate Professor of Cancer Biology at Vanderbilt University School of Medicine:

This could be problematic especially for the Johnson & Johnson (J&J) vaccine. It has been suggested by members of the vaccine committee that the J&J vaccine could be distributed as a 2-dose product instead of a single-dose vaccine because evidence suggests a more robust immune response comes with 2 doses. Evidence also suggests that there is a more robust immune response when the second does for a single-shot J&J vaccine is Moderna or Pfizer-BioNTech. This provides a growing body of evidence that supports the notion that mixing and matching of the J&J vaccine is warranted due the stronger immune response induced by the Pfizer or Modern vaccines as the second component to the J&J single dose.

What role will this all play in FDA approval and CDC guidance will be interesting going forward. The mild storage temperature and the single dose advantages of the J&J vaccine as well as the 15M people that have been vaccinated will be debated against its usefulness in the future in the US.

William Schaffner, MD, Professor of Preventive Medicine at Vanderbilt University Medical Center:

Very quickly said: I’m for it. I’ve seen the data, and I would hope the (FDA) and the CDC are also impressed with the data. Clearly, if you’ve received the J&J dose and then you received one of the mRNA vaccines, you get a very large boost in antibody—even more antibody than if you got a second dose of J&J. So I would think that that would be the best for all the J&J recipients, ands would also make the vaccine more readily available in many, many more locations—because J&J vaccines are not available in a widespread fashion any more. It had the initial attraction of being the “one and done” vaccine—except it’s not “one and done.” And so, much less is being used than once was.

Clearly, the folks who received J&J are showing more of a diminution in protection than the folks who receive Moderna and Pfizer. And once it becomes official, very shortly, I would certainly urge everyone to go ahead and get another vaccine. And if at that time, mix and match was also available to those folks, that’s the direction I would be recommending my patients go.

Carlos del Rio, MD, Executive Associate Dean of Emory School of Medicine & Grady Health System:

As far as Johnson & Johnson, I think the recommendation is going to be that everyone who got a Johnson & Johnson vaccine get a booster 2 months after. So that’s gong to be a little different. I think it’s the right decision to make. The question is what should be the booster, and Johnson & Johnson showed data with a second shot of Johnson & Johnson. But the data from the mix and match trial show you’re better off, and at least get a better immune response, if you get an mRNA vaccine after you get the Johnson & Johnson.

The data from the mix and match suggest it is safe to do that; it does not say it is more effective from a clinical standpoint because we don’t have that data. So I want to caution people that, just because the numbers look better in the lab or the data looks very impressive, that doesn’t translate into clinical benefit. Again, at the end of the day, it could be very effective—and they continue to do what they were designed to do, which is to prevent severe disease and hospitalization.