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 received mRNA vaccines are boosted with an adenovirus-based vaccine, the report said.

Writing in JAMA Network Open, 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) prompt neutralizing antibody responses (NAb). However, both also have drawbacks. While the mRNA vaccine induces higher initial NAb titers, the response tends to be less durable than that of the Janssen vaccine.

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

The participants in the study ranged in age from 23-84 years, though most were female (82%) and White (78%).

Both booster shots helped protect patients against SARS-CoV-2 variants of concern. The Pfizer/BioNTech shot led to a peak median titer of 1,018 Omicron neutralizing antibodies at week 2, but that level fell to a median titer of 148 by week 16. The Janssen booster took longer to achieve a peak response but also led to a more durable response. In patients boosted with that vaccine, the median titer level peaked at 859 antibodies at week 4, but the median number was 403 by 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 can 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 just 4 months of follow-up. They said larger studies with longer follow-up times would be required to find out whether the results were generalizable and durable.

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

“These data suggest potential immunologic benefits of mix-and-match heterologous COVID-19 vaccine regimens and emphasizes the importance of durability for COVID-19 vaccine boosting strategies,” they concluded. “Future studies could explore reduced booster doses as well as Omicron-containing boosters.”