Study shows potential benefits of mix-and-match approach for COVID-19 boosters

Key takeaways:

• Receiving a booster dose of either the Pfizer-BioNTech or Johnson & Johnson vaccine increased immune responses in people who previously received the Pfizer-BioNTech vaccine.
• The homologous approach led to a rapid increase in omicron-neutralizing antibodies that peaked at week 2 and declined nearly seven-fold by week 16.
• The heterologous approach was associated with an increase in omicron-neutralizing antibodies that peaked at week 4 and declined about two-fold by week 16.

A “mix-and-match” strategy for COVID-19 vaccine boosters may help improve the durability of antibody and T-cell responses against the Omicron variant of SARS-CoV-2, according to researchers.

Specifically, C. Sabrina Tan, MD, an assistant professor of medicine at Harvard Medical School, and colleagues found that people who received a booster dose of an adenovirus vector vaccine (Johnson & Johnson) after primary immunization with a messenger RNA vaccine (Pfizer-BioNTech) had durable responses for at least 4 months.

“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,” the researchers wrote.

The cohort study included 68 participants who received two doses of the Pfizer-BioNTech vaccine and were boosted 6 months later with either the Pfizer-BioNTech or Johnson & Johnson vaccine. Of the participants, 82% were women, 78% were white, 10% were Asian, 6% were Black and 6% were Hispanic or Latino.

The researchers assessed humoral immune responses for 16 weeks after the booster dose was administered. They also evaluated CD8+ and CD4+ T-cell responses with an intracellular cytokine straining assay.

Tan and colleagues found that boosting with the Johnson & Johnson vaccine was linked to an increase in median omicron-neutralizing antibody titers, which rose from 21 (interquartile range, 20-32) at week 0 to 591 (IQR, 272-881) at week 2. The titers peaked at week 4 at 859 (IQR, 467-1,838) before declining 2.1-fold to 403 (IQR, 208-1,130) at week 16. Further, the researchers wrote that this approach was associated with increased Omicron-specific CD8+ T-cell responses.

For the Pfizer-BioNTech booster group, the researchers found a rapid increase in omicron-neutralizing antibodies, which peaked after 2 weeks at a median titer of 1,018 (IQR, 699-1,646). They then decreased to a median titer of 148 (IQR, 95-266) — a 6.9-fold decline — at week 16.

Because the homologous approach resulted in a steeper decline in antibody titers than the heterologous approach, Tan and colleagues wrote that the data suggest “improved durability of the heterologous boosting approach.”

“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 findings build on a previous study examining the mix-and-match booster strategy, “which evaluated a shorter boosting interval of 3 to 4 months, although this prior study only reported responses at 2 to 4 weeks following the boost,” the researchers wrote.

Although multiple studies have shown that three mRNA vaccine doses effectively induce Omicron-neutralizing antibody titers, the benefits decrease with time. After a fourth mRNA vaccine dose, Tan and colleagues noted that the protective efficacy against SARS-CoV-2 infection “has been shown to wane even more quickly.”

“Such rapid waning of immunity has led to recommendations for frequent mRNA vaccine boosting, which may be challenging to sustain as a long-term policy in the developed world and difficult to implement in the developing world,” the researchers wrote. “The development of boosting strategies with improved durability would, therefore, be desirable.”