Publication date: Nov 11, 2024

The durability of Hybrid immunity induced by natural infection and/or COVID-19 vaccines and evidence supporting further booster vaccination are crucial factors for pandemic response, yet remain poorly understood. We measured the durability of immune response and neutralizing capacity of antibodies following Homologous/Heterologous vaccination by mRNA-based vaccines (Pfizer-BioNTech BNT162b2) or (Moderna mRNA-1273) and viral vector-based vaccines (ChAdox1 nCoV-19-Oxford-AstraZeneca) in infected and non-infected patients. We also evaluated the long-lasting specific humoral IgG levels and T-cell immunity of the Memory CD8 cells. We found that heterologous prime boosters led to significantly higher IgG antibody levels)9. 09(than homologous boosters)5. 236) one year after vaccination. We measured SARS-CoV-2 anti-S IgG antibodies and then assessed their neutralizing capacity to inhibit the receptor-binding domain (RBD) of the SARS-CoV-2 wild-type strain and omicron B. 1.1. 529/BA. 2 variants from binding to the ACE2 receptors. The heterologous regiment demonstrated superior ACE2-binding inhibition and consistently had higher mean ACE2-receptor binding inhibition across all dose regimens without the need for further doses. The CD8+ T cells producing IFN-γ to various COVID-19 vaccine dose regimens were evaluated. We found that robust T cell mediated immune responses were preserved and largely induced by a heterogeneous vaccination eliciting a significantly higher CD8+ T cells IFN-γ response in 100% of vaccinees regardless of previous natural infection. Indeed, the difference between infected and nacEFve groups was less pronounced suggesting a reduced infection-related response. Across three layers of evidence, this study showed that heterologous vaccination provides longer-lasting immunity than homologous doses, regardless of prior natural infection.

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