New Study Suggests Potential for Heterologous COVID-19 Boosters


A recent study suggests that homologous and heterologous vaccines protect against the Omicron variant of COVID-19, but the heterologous appears more durable.

Both the heterologous (Ad26.COV2.S) and homologous messenger RNA (mRNA) COVID-19 vaccine boosters (BNT162b2) increased Omicron-specific antibody and T-cell immune responses in BNT162b2 vaccinated individuals. However, those boosted with the BNT162b2 vaccine experienced a rapid increase in antibodies that decreased quickly, whereas those boosted with the Ad26.COV2.S vaccine had longer lasting Omicron neutralizing antibodies, according to the results of a recent study.

mRNA vaccines for COVID-19 offer effective protection against the virus. Although getting a third dose of the BNT162b2 mRNA vaccine increased virus-fighting neutralizing antibodies (NAbs), the effects only lasted 3-6 months. A fourth dose increased protection against Omicron for less time than the third vaccine. The adenovirus serotype 26 vector-based COVID-19 vaccine (Ad26.COV2.S) produced less concentrated NAbs, but the antibodies were effective and durable for at least 8 months, according to the study.

Researchers sought more information on the optimal boosting strategies for the Omicron variant, looking at the immunogenicity and durability of heterologous vs homologous vaccine boosting strategies.

The team performed a cohort study of 68 diverse participants at Beth Israel Deaconess Medical Center (BIDMC) in Boston over 16 weeks between August and October 2021. These individuals received full vaccinations of BNT162b2(Pfizer-BioNTech) within the past 6 months and were evaluated for NAbs and T-cell response after being boosted with either Ad26.COV2.S (Janssen) or BNT162b2.

Among the participants, 82% were female, 78% were White, and the median age was about 35 years of age. The researchers either vaccinated participants with the Ad26.COV2.S or BNT162b2 booster and, for 4 months, assessed humoral immune response through NAb assays, and cellular immune response from CD8+ and CD4+ T-cell responses.

Both the heterologous and homologous boosters were associated with increased Omicron-specific humoral and cellular immune responses in previously vaccinated individuals. The mRNA booster rapidly increased the Omicron NAbs until the second week, where it declined after about 4 months.

The Ad26.COV2 booster vaccine increased the concentration of Omicron NAbs until week 4, peaking and declining approximately 2-fold by the fourth month. This suggests the heterologous adenovirus vaccine is more durable than the homologous mRNA vaccine, according to the researchers.

The Ad26.COV2 booster was also associated with higher CD8+ T-cell responses, which can protect against severe COVID-19 symptoms.

“Moreover, cellular immune responses have shown greater durability and more cross-reactivity against SARS-CoV-2 variants than serum NAb responses, suggesting their importance for protection against virus variants such as Omicron that largely escape NAb responses,” the study authors wrote.

The study was limited by the small sample size, unrandomized format, and inequal female/male ratio, according to the authors. Participants were also generalized to the greater Boston area, limiting the demographic diversity, and the immunogenicity data only goes up to 4 months, so further assessment should look at long-term durability.

No serious adverse effects occurred with either booster.

“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 study authors concluded.


Tan, Sabrina, Collier, Ai-ris, Yu, Jingyou, et al. Durability of Heterologous and Homologous COVID-19 Vaccine Boosts. Aug 10, 2022. Accessed Aug 11, 2022.

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