Sorting Out the New COVID Vaccine Booster Recommendations

Sandra Adamson Fryhofer, MD


October 27, 2021

This transcript has been edited for clarity.

This episode of Medicine Matters addresses the need for boosters for those fully vaccinated with Moderna and Janssen COVID vaccines and explains who needs a booster, which one to get, and when a booster is needed.

We're in a pandemic. The Delta variant is dominant and it is a superspreader. Fortunately, we have three safe and highly effective COVID vaccines. However, studies show some waning of immunity with time and during the Delta period. We're also seeing greater declines in vaccine effectiveness in older patients. Boosters can help restore and build immune response to more protective levels. Boosters have already been authorized for many of the nearly 105 million who got the Pfizer vaccine. Boosters are now available for the 70 million fully vaccinated with Moderna vaccine, and for the 15 million Americans who received a single dose of Janssen COVID vaccine.

The Vaccines and Related Biological Products Advisory Committee, FDA's independent advisory committee, met for 2 days in mid-October. In less than a week, FDA released its authorization decision on regulatory allowance. CDC's Advisory Committee on Immunization Practices met the following day, October 21st, and voted. A few hours later, CDC's director announced the new interim recommendations.

Moderna wanted what Pfizer already had and got it: a recommendation for a booster dose at least 6 months after a primary series. Janssen got what it wanted, too: a recommendation for a booster dose at least 2 months after a single Janssen vaccine dose.

Mixing and Matching Boosters

FDA's allowance to mix and match the kind of booster and original vaccine was incorporated in CDC's final recommendations. This makes choosing how to boost more flexible, convenient, and potentially more personalized. The language in CDC's new recommendation for the kind of booster is sort of vague. It doesn't specify the kind of booster shot to give. You can essentially boost with any authorized COVID vaccine. It allows for both homologous boosting (the booster and the original vaccine match) and heterologous boosting (the booster and the primary vaccine series are different). Either kind of boost is permitted.

To get a booster, it's the honor system. If people say they‘re eligible, they can get it.

Booster recommendations for both mRNA COVID vaccines have been harmonized. Boosters at least 6 months after a primary mRNA vaccine series (for both Pfizer and now Moderna) only apply to certain adults, and you must be at least 65, have health issues, or have a high-exposure job or living conditions to qualify. The same risk groups and the same 6-month time interval after the primary series apply to both mRNA vaccines. But the size of the booster dose is different. A Pfizer booster is a full Pfizer dose, which is 30 µg. A Moderna booster is half of a full dose, which is 50 µg. The Moderna half-dose boost is less reactogenic as compared with a full-dose Moderna vaccine dose (100 µg).

For adults (18 and older) who received a Janssen COVID vaccine, a booster is recommended at least 2 months after a single-dose Janssen primary series. This more universal recommendation applies to everyone 18 and older who received it. This broad eligibility is due to Janssen's lower vaccine effectiveness as compared to mRNA vaccines. The boost can help increase Janssen vaccine effectiveness. You can mix and match when it comes to picking the kind of booster to give.

FDA's allowance for the mix-and-match boosting option is supported by NIH's NIAID ongoing mix-and-match study. This study tested and compared different combinations. It mixed and matched different primary COVID vaccine series with the same and with different kinds of boosters. Boosters of any of the three vaccines increased neutralizing antibody titers, irrespective of the kind of booster or the kind of primary vaccine series. The study is small and is not powered to compare booster types. However, Moderna and Pfizer boosters did seem to do a better job at boosting and triggered stronger antibody responses than Janssen boosters. Cellular immunity is also being analyzed. The various combinations revealed no new safety concerns. Reactogenicity and adverse events were similar across booster groups. This is very reassuring.

Being able to mix and match boosters and primary series greatly increases flexibility. It gives patients and physicians more input in the process. You can choose the booster vaccine depending on the kind of vaccine available and potential vaccine reactions. Risk for vaccine-specific adverse reactions in certain age groups as well as sex-based differences could be considered: For example, Janssen vaccine has been linked to thrombosis with thrombocytopenia syndrome (TTS). TTS risk is higher in females under 50. On the other hand, mRNA vaccines have been linked to myocarditis. Risk is highest in young males 18-25, particularly after the second dose. Fortunately, Israeli data have not shown an even higher risk for myocarditis after a third mRNA vaccine dose. These types of concerns can be considered when choosing the kind of booster vaccine.

In summary, this mix-and-match booster option gives us the flexibility we need for efficient and effective vaccination programs. Look for further CDC guidance for selecting the best type of boost for particular patients in its clinical considerations section on the CDC website. Boosting can help maintain and increase protection, but we can't lose sight of our most important goal: vaccinating the more than 65 million Americans who remain unvaccinated.

For Medicine Matters, I'm Dr Sandra Fryhofer.

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