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Correlates of Durability and Boosting Following Ad26.COV2.S Immunization in Rhesus Macaques

ABSTRACT: Ad26.COV2.S is a single-shot vaccine with clinical efficacy against symptomatic COVID-19. 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 8-10 months following the initial immunization. Innate immune responses, memory B cell responses, and bone marrow plasma cell responses correlated with durable antibody responses following initial vaccination. Following Ad26.COV2.S boost immunization, binding and neutralizing antibody responses increased 31-69 fold and 23-43 fold, respectively, compared with pre-boost levels against multiple SARS-CoV-2 variants, including the delta variant. Antigen-specific B cell and T cell responses also increased. Humoral and cellular immune responses were largely comparable for ancestral, alpha, beta, gamma, delta, and kappa SARS-CoV-2 variants following the boost immunization. Boosting with a modified Ad26.COV2.S.351 vaccine expressing the SARS-CoV-2 beta Spike led to largely comparable responses. These data demonstrate that a late boost with Ad26.COV2.S in rhesus macaques resulted in a dramatic increase in humoral and cellular immune responses that were highly cross-reactive across multiple SARS-CoV-2 variants.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE193264 | GEO | 2022/02/10

REPOSITORIES: GEO

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Ad26.COV2.S Prevents SARS-CoV-2 Induced Pathways of Inflammation and Thrombosis in Hamsters

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Project description:Thrombosis with thrombocytopenia syndrome (TTS) is an extremely rare but potentially serious adverse event following immunization with the adenovirus vector-based COVID-19 vaccines Ad26.COV2.S (Janssen / Johnson & Johnson) or ChAdOx1 (AstraZeneca). However, no cases of TTS have been reported in over 1.5 million individuals who received a second immunization with Ad26.COV2.S in the United States, suggesting that anti-vector immunity may reduce TTS risk. Here we show robust stimulation of platelet activation and coagulation pathways and innate immune pathways in patients with TTS but only transient activation of these pathways following vaccination. We evaluated proteomic profiles in 2 patients with TTS and transcriptomic and proteomic profiles in 20 people following an initial dose and a booster dose of Ad26.COV2.S and in 14 people who received the mRNA vaccines BNT162b2 or mRNA-1273. Initial Ad26.COV2.S vaccination induced transient activation of platelet activation and coagulation pathways and innate proinflammatory pathways that resolved by day 7. TTS patients showed enhanced and sustained upregulation of these pathways, whereas a second immunization with Ad26.COV2.S or a reduced initial dose of Ad26.COV2.S resulted in lower activation of these pathways. These data provide insight into TTS pathogenesis and suggest a potential strategy for reducing TTS risk by lowering the dose of Ad26.COV2.S.

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Correlates of Durability and Boosting Following Ad26.COV2.S Immunization in Rhesus Macaques

Project description:Correlates of Durability and Boosting Following Ad26.COV2.S Immunization in Rhesus Macaques

| PRJNA795508 | ENA

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