Abstract
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.
Highlights
The Ad26.COV2.S vaccine is a replication-incompetent adenovirus (Ad) 26 vector [1] expressing the stabilized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein [2] from the Wuhan 2019 strain, which is identical to the spike protein from the WA1/2020 strain
We evaluated the correlates of durability of single-shot Ad26.COV2.S vaccination in rhesus macaques and the immunogenicity of a late boost at 8-10 months with Ad26.COV2.S or Ad26.COV2.S.351, which expresses the stabilized SARSCoV-2 Spike protein from the B.1.351 variant
Receptor binding domain (RBD)-specific binding antibody responses were assessed by enzyme-linked immunosorbent assay (ELISA, Fig. 2A) [4, 20, 21]
Summary
The Ad26.COV2.S vaccine is a replication-incompetent adenovirus (Ad) 26 vector [1] expressing the stabilized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein [2] from the Wuhan 2019 strain, which is identical to the spike protein from the WA1/2020 strain. Immunogenicity and protective efficacy of the single-shot Ad26.COV2.S vaccine has been demonstrated in hamsters and rhesus macaques [3,4,5,6] as well as in humans [4, 7,8,9,10,11]. Recent data has shown durability of immune responses induced by single-shot Ad26.COV2.S in humans for at least 8 months [12]. We evaluated the correlates of durability of single-shot Ad26.COV2.S vaccination in rhesus macaques and the immunogenicity of a late boost at 8-10 months with Ad26.COV2.S or Ad26.COV2.S.351, which expresses the stabilized SARSCoV-2 Spike protein from the B.1.351 (beta) variant
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