GSE193264
A homologous or variant booster vaccine after Ad26.COV2.S immunization enhances SARS-CoV-2-specific immune responses in rhesus macaques
Ad26.COV2.S has demonstrated durability and clinical efficacy against symptomatic COVID-19 in humans. In this study, we report the correlates of durability of humoral and cellular immune responses in 20 rhesus macaques immunized with single-shot Ad26.COV2.S and the immunogenicity of a booster shot at 8 to 10 months after the initial immunization. Ad26.COV2.S elicited durable binding and neutralizing antibodies as well as memory B cells and long-lived bone marrow plasma cells. Innate immune responses and bone marrow plasma cell responses correlated with durable antibody responses. After Ad26.COV2.S boost immunization, binding and neutralizing antibody responses against multiple SARS-CoV-2 variants increased 31- to 69-fold and 23- to 43-fold, respectively, compared with preboost concentrations. Antigen-specific B cell and T cell responses also increased substantially after the boost immunization. Boosting with a modified Ad26.COV2.S.351 vaccine expressing the SARS-CoV-2 spike protein from the beta variant led to largely comparable responses with slightly higher beta- and omicron-specific humoral immune responses. These data demonstrate that a late boost with Ad26.COV2.S or Ad26.COV2.S.351 resulted in a marked increase in humoral and cellular immune responses that were highly cross-reactive across multiple SARS-CoV-2 variants in rhesus macaques. Overall design: Twenty-four outbred Indian-origin adult male and female rhesus macaques (Macaca mulatta) aged 4 to 22 years were randomly allocated to groups. Sample size and age criteria were determined on the basis of the results of previous nonhuman primate studies. All animals were housed at BIOQUAL Inc. Animals were immunized with 10^11 vp (n = 10) or 5 × 10^10 vp (n = 10) Ad26.COV2.S and were followed for either 230 or 315 days. Four unvaccinated animals were used as controls. The vaccinated animals were then boosted with 5 × 10^10 vp Ad26.COV2.S (n = 10) or Ad26.COV2.S.351 (n = 10). Half of the animals in each original dose group were immunized by each booster vaccine. All immunologic studies were performed blinded. No data points were omitted from analysis. Animal studies were conducted in compliance with all relevant local, state, and federal regulations and were approved by the BIOQUAL Institutional Animal Care and Use Committee.