Report Finds “Mix-and-Match” COVID-19 Booster Approach More Effective

Booster shots of coronavirus disease 2019 (COVID-19) vaccines lead to an increase in neutralizing antibodies against the Omicron variant of the SARS-CoV-2 virus, according to a new study, but a stronger response is generated when patients who initially receive mRNA vaccines were boosted with an adenovirus-based vaccine, the report said.

Sign up JAMA network opened, corresponding author Dan H. Barouch, MD, PhD, of Beth Israel Deaconess Medical Center, and colleagues, explained that both the Pfizer/BioNTech vaccine (a two-dose mRNA vaccine called BNT162b2) and the Janssen adenovirus serotype 26 vector-based vaccine (called Ad26.COV2.S) lead to neutralizing antibody reactions (NAb). However, both also have drawbacks. Although the mRNA vaccine induces higher initial NAb titers, the response is generally less durable than that of the Janssen vaccine.

The researchers wanted to know whether the type of booster administered to a patient could affect the level and duration of their protection against COVID-19 and in particular against the Omicron variant. To find out, they recruited 68 people who had received the first 2-dose Pfizer/BioNTech mRNA vaccination at least 6 months earlier. Forty-one patients received a booster vaccination with the Janssen vaccine and the remaining 27 received an additional dose of the Pfizer BioNTech vaccine. Enrollment took place between August and October 2021 and immune responses were monitored for 14 weeks after the booster dose.

The study participants ranged in age from 23-84 years, although most were women (82%) and whites (78%).

Both booster shots helped protect patients from SARS-CoV-2 variants of concern. The Pfizer/BioNTech injection resulted in a peak median titer of 1,018 Omicron neutralizing antibodies at week 2, but that level dropped to a median titer of 148 at week 16. The Janssen booster took longer to reach a peak response, but also led to a more sustained response. In patients boosted with that vaccine, the median titer level peaked at 859 antibodies at week 4, but the median number was 403 at week 16.

Barouch and colleagues said these data appear to support the “mix-and-match” approach to booster doses.

“We speculate that the differences in the kinetics of the immune responses may be related to differences in the kinetics of immunogen expression in vivo,” they wrote.

The Janssen booster also led to superior increases in CD8+ T cells, which some evidence suggests may also be protective against SARS-CoV-2, especially when NAb responses are insufficient.

The authors said their study has significant limitations. Among them, it was done in a small study population, at a single site, and with only 4 months of follow-up. They said larger studies with longer follow-up times would be needed to find out if the results were generalizable and sustainable.

Still, they said the data highlights the benefits of having different types of vaccines and of using those different types strategically.

“These data suggest potential immunological benefits of mix-and-match heterologous COVID-19 vaccine regimens and highlight the importance of sustainability for strategies for boosting COVID-19 vaccines,” they concluded. “Future studies could investigate both reduced booster doses and Omicron-containing boosters.”