Home Cellular health Superior protection with COVID-19 “mix-and-match” booster strategy

Superior protection with COVID-19 “mix-and-match” booster strategy


The coronavirus disease 2019 (COVID-19) pandemic was caused by the sudden global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since SARS-CoV-2 emerged in late 2019, scientists have worked tirelessly to develop multiple vaccines to reduce SARS-CoV-2 transmission and protect individuals from severe COVID-19.

Recently, a rapid decline in antibody levels induced by vaccination with messenger ribonucleic acid (mRNA) vaccines has been observed. in a new Open Jama Network study, researchers discuss the durability and immunogenicity of homologous and heterologous booster regimens with Johnson & Johnson Ad26.COV2.S and Pfizer-BioNTech BNT162b2 vaccines.

Study: Durability of heterologous and homologous COVID-19 vaccine boosters. Image Credit: PhotobyTawat / Shutterstock.com


Exceptional short-term immunogenicity and protective efficacy have been associated with COVID-19 mRNA vaccines. However, between three and six months after the primary vaccination, neutralizing antibody (nAb) responses decline. A similar drop in nAb levels was observed after the third and fourth mRNA booster doses which were proposed to provide protection against the highly mutated variant of Omicron.

Compared to mRNA vaccines, lower initial nAb titers are induced by the Johnson & Johnson adenovirus vector-based Ad26.COV2.S vaccine against COVID-19. However, these responses were maintained for at least eight months.

Previous research has shown that CD8+ T cell responses may contribute to protection against serious disease and are more durable than serum nAb titers. T-cell responses show significant cross-reactivity against the Omicron variant, despite the ability of this variant to evade vaccination-induced antibody traps.

Optimal recovery strategies are the subject of active research, the results of which will be decisive for the long-term control of the pandemic.

About the study

The main objective of this study was to analyze the durability and immunogenicity of homologous and heterologous vaccine booster strategies.

This study was conducted at a clinical site in Boston, Massachusetts. Taken together, 68 study participants who received two doses of the BNT162b2 vaccine and who received a booster with the BNT162b2 or Ad26.COV2.S vaccines at least six months after completing their primary vaccination course were included in the current study.

People with a history of SARS-CoV-2 infection, as well as receipt of other COVID-19 vaccines or immunosuppressive drugs, were excluded from the study. Additionally, individuals were not permitted to participate if they had confirmed SARS-CoV-2 infection or positive nucleocapsid serology detected by electrochemiluminescence (ECLA) testing.

Study participants were recruited between August 12, 2021 and October 25, 2021, with an additional four months of follow-up after the end of the study period. Data analysis to assess humoral and cellular immune responses was performed between November 2021 and February 2022.

Study results

The homologous boost generated a rapid increase in Omicron nAbs, which peaked in week 2 and then declined nearly seven-fold by 16e the week. Comparatively, boosted heterologous nAbs peaked in week 4 and declined approximately two-fold by 16e the week. These results are consistent with other findings describing the durability of immune responses after initial mRNA vaccination with a booster dose of the Ad26.COV2.S vaccine.

The heterologous booster dose was also associated with higher Omicron-specific CD8+ T cell responses. This response remains highly reactive against the Omicron variant, despite the ability of this variant to escape vaccination-induced traps.

In South Africa, the BNT162b2 and Ad26.COV2.S vaccines provided 70% and 85% efficacy, respectively, against hospitalization with the Omicron variant in the absence of nAbs. This observation suggests the crucial role of other immune responses in protecting against severe COVID-19.


A key limitation of the current study is its small size at a single site in Boston. In addition, there was a lack of randomization and women were overrepresented.

Thus, future research using larger and more representative samples is needed. Additionally, follow-up times beyond 16 weeks are required to assess long-term durability.


Taken together, heterologous and homologous booster vaccination elicited Omicron-specific antibody and T cell responses in mRNA vaccinated individuals. Notably, heterologous vaccination elicited higher nAb and CD8+ T cell responses. These observations suggest the advantages of heterologous vaccine regimens.