A viral vector prime and protein boost vaccine regimen elicits higher binding antibody titers than a homologous viral vector prime-boost regimen.

(SARS-CoV-2) has infected a large fraction of the human population. Currently, most individuals have developed immunity either through vaccination or natural infection. Despite this, SARS-CoV-2 booster immunizations are still recommended to reduce the risk of reinfections, but there is still limited understanding of how different booster vaccine platforms influence antibody responses. We conducted immunological studies in mice to evaluate the boosting effects of different vaccine platforms on antibody responses. C57BL/6 mice were first primed with an adenovirus serotype 5 (Ad5) vector vaccine expressing the SARS-CoV-2 spike protein. The mice were then boosted with the same Ad5-based vaccine (homologous boosting) or with a protein-based vaccine (heterologous boosting). Interestingly, the heterologous regimen (Ad5 prime/Protein boost) elicited higher binding antibody responses, relative to the homologous regimen (Ad5 prime/Ad5 boost). Similar potentiation of antibody titers was reported when mice were primed with poxvirus or rhabdovirus vectors and then boosted with protein. These findings highlight a potential advantage of protein booster immunizations to potentiate humoral immunity.