Boosters, Half Doses and Mix-Matches: Microbial Minutes

Nov. 17, 2021

Is Mixing-and-Matching safe and effective? Which COVID-19 vaccine is best? And do differences in dosage and wait times between doses impact vaccine performance?

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ASM presents Microbial Minutes, a monthly video series of trending topics in the microbial sciences.

Although COVID-19 vaccines continue to remain highly effective, the number of breakthrough infections has increased since the emergence of the Delta variant, and the longevity of vaccine induced immunity is still uncertain. Antigenic evolution of the virus, bolstered by coinciding evidence of antibody waning in some vaccinated host populations, has prompted the FDA to issue Emergency Use Authorization (EUA) for booster doses of Pfizer, Moderna and Johnson & Johnson vaccines.

The simultaneous announcement that people will be given the option to choose a different vaccine for their booster than they received during primary vaccination - also known as heterologous booster vaccination, or mixing-and-matching vaccines - has resurfaced familiar questions about whether any one vaccine (or vaccine combo) is superior to the others. Now, 9 possible vaccine combinations are available in the U.S., and many are trying to decide if mixing-and-matching is safe and effective, and if so, which booster they should choose. 

In this Microbial Minutes, we begin to address some of these questions by taking a look at the preliminary study used to inform FDA heterologous booster recommendations. 

Why Boosters?

Falsey A.R. et al. SARS-CoV-2 Neutralization with BNT162b2 Vaccine Dose 3. The New England Journal of Medicine. Sept. 15, 2021.

Is there precedent for Mixing and Matching? 

Borobia A.M. et al. Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): a multicentre, open-label, randomised, controlled, phase 2 trial. The Lancet. July 10. 2021.

Shaw R.H. et al. Heterologous prime-boost COVID-19 vaccination: initial reactogenicity data. The Lancet. May 29, 2021

Is Mixing and Matching COVID-19 Vaccine Boosters Safe and Effective?

Atmar R.L. et al. Heterologous SARS-CoV-2 Booster Vaccinations – Preliminary Report. medRxiv. Oct. 15, 2021.

Do Dosages and Wait Times Matter?

Robles Font├ín M.M. et al. Time-Varying Effectiveness of Three Covid-19 Vaccines in Puerto Rico. medRxiv. Oct. 20, 2021.

Gutman R. Is Moderna Really Better Than Pfizer—Or Is It Just a Higher Dose?. The Atlantic. Oct. 28, 2021.

Take-Away Points

  • All 3 boosters are effective at increasing antibody binding and neutralizing activity against SARS-CoV-2 antigens.
  • Reactogenicity did not differ between heterologous and homologous boosts, and no significant safety concerns were identified in this study.
  • Those who received the Moderna vaccine during primary vaccination experienced the highest levels of binding activity and the highest levels of neutralization activity. 
  • Those who received the Johnson & Johnson vaccine for primary vaccination experienced the largest fold increase in binding activity, as well as neutralization activity. 
  • Vaccine dosage and wait time between doses are important factors when it comes to vaccine efficacy. These factors are also under investigation.

Author: Ashley Hagen, M.S.

Ashley Hagen, M.S.
Ashley Hagen, M.S. is the Scientific and Digital Editor for the American Society for Microbiology and host of ASM's Microbial Minutes.