Last week, both the Federal Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) recommended COVID-19 booster vaccinations in specific populations and also endorsed a “mix-and-match” approach. This would allow healthcare  providers to administer a different booster shot to individuals than the one initially received. Why was this decision made and what is the science behind it?

Heterologous Prime-Boost Strategy

Many vaccines are administered in a multi-dose series with the same vaccine, known as a homologous approach. The first dose will spur the immune system’s B cells to create antibodies against a pathogen and incite T cells to recognize and destroy infected cells. A second dose will often increase and intensify these immune responses. The polio vaccine requires a four-dose series while the diphtheria, tetanus and pertussis combined vaccines require a five-dose series and a booster to confer full immunity. In international COVID-19 studies, a heterologous prime-boost strategy has been employed in which one vaccine is used as the primary dose and an alternative vaccine as the second dose. Research conducted by Nordström, Ballin & Nordström (2021) found that this type of vaccination schedule is an “effective alternative to increase population immunity against COVID-19.” Their investigation, which used a viral vector vaccine (Oxford/AstraZeneca approved for emergency use in Europe) as the primary dose and an mRNA vaccine (either Pfizer/BioNTech or Moderna) as the second dose, was associated with 67% to 79% effectiveness against symptomatic COVID-19 infection compared with the 50% effectiveness using the same viral vector vaccine alone.
 
Mixing vaccines has the potential to produce broader and stronger responses than a single vaccine, and different types stimulate the immune system in different ways (Zimmer, 2021). In the U.S., while research is limited, early data suggests that booster doses of the mRNA vaccines, Moderna or Pfizer-BioNTech, were more effective in increasing antibody levels compared to the Janssen/Johnson & Johnson (J&J) vaccine (Mandavilli, 2021). Data from a study conducted by Atmar et al. (2021) found that the Janssen/J&J vaccine increased antibodies just fourfold, while a Pfizer-BioNTech booster improved antibody levels by a factor of 35 and a Moderna booster raised levels 76-fold. This study, however, is preliminary and has not yet been peer-reviewed.
 
The recommendation for a booster focuses on the elderly and high-risk individuals. Endorsement of a mix-and-match strategy provides more flexibility with respect to ease of access and availability at local pharmacies and provider offices. However, the FDA and CDC do not recommend one vaccine booster over another and instead will allow healthcare providers and individuals to make decisions based on the data available.
 
Information regarding COVID-19 infection, its variants, and vaccines continue to evolve. We will do our best to keep you up to date on the latest recommendations as they become available.
 

References
 
Atmar, R.L., Lyke, K.E., Deming, M.E., Jackson, L.A., Branche, A.R., El Sahly, A.M. et al. (2021). Heterologous SARS-CoV-2 Booster Vaccinations – Preliminary Report. medRxiv. https://doi.org/10.1101/2021.10.10.21264827
 
Mandavilli, A. (2021, October 21). C.D.C. Recommends Covid booster shots for millions of Americans. The New York Times. Retrieved October 22, 2021 from https://www.nytimes.com/2021/10/21/health/covid-vaccine-boosters-cdc.html?campaign_id=9&emc=edit_nn_20211022&instance_id=43489&nl=the-morning&regi_id=114109069&segment_id=72340&te=1&user_id=bccf198aa4bd46687e8247e8484c42b3
 
Nordstrom, P., Ballin, M. & Nordstrom, A. (2021). Effectiveness of heterologous ChAdOx1 nCoV-19 and mRNA prime-boost vaccination against symptomatic Covid-19 infection in Sweden: A nationwide cohort study. The Lancet Regional Health. https://doi.org/10.1016/j.lanepe.2021.100249  
 
Zimmer, C. (2021, October 19). Mix-and-match Covid boosters: Whey they just might work. The New York Times. Retrieved on October 22, 2021 from https://www.nytimes.com/2021/10/19/health/covid-vaccine-mix-match.html