Impact of Pre-Existing Adenovirus Immunity on Vaccine Immunity Induced by ChAdOx1 nCoV-19 in Immunodeficient Patients 2330644

Abstract Introduction Chimpanzee adenovirus—vectored COVID-19 vaccines, including ChAdOx1 nCoV-19 (nCoV-19), were selected in part due to low seroprevalence in humans. However, the impact of pre-existing immunity to human adenoviruses on immune responses to these vaccines remains incompletely understood. We investigated immunological cross-reactivity between ChAdOx1 and human adenovirus type 5 (HuAd5) and tested the hypothesis that pre-existing HuAd5-specific T cells may enhance SARS-CoV-2 spike-specific T cell responses following nCoV-19 vaccination in antibody-deficient individuals. Methods We analyzed samples from healthcare workers and immunodeficient patients vaccinated with either nCoV-19 or BNT162b2. HuAd5 hexon-specific T cells responses were assessed using IFN-γ ELISpot and flow cytometry. Anti-HuAd5 heron antibodies were measured using Luminex for IgG and a GFP-expressing HuAd5 neutralization assay for neutralizing activity. Findings from the current study were compared with previously published COVID-19 vaccine response data in these cohorts. Results We observed significant T cell and antibody cross-reactivity between ChAdOx1 and HuAd5. In immunodeficient individuals vaccinated with nCoV-19 HuAd5 hexon-specific T cell frequencies were positively associated with SARS-CoV-2 spike-specific T cell responses, an association not observed in BNT162b2 recipients. Conversely, higher anti-HuAd5 hexon antibody levels were inversely correlated with spike-specific T cell responses in the nCoV-19 cohort. Conclusion These findings support a model in which heterologous pre-existing adenovirus-specific T cell immunity contributes to enhanced spike-specific T cell responses following adenovirus-vectored vaccination in antibody deficient individuals. This bystander T cell effect provides an explanation for the observation in several studies of higher T cells response to adenovirus-vectored COVID-19 vaccines compared to mRNA vaccines in immunodeficient or elderly patients. Funding Source NIHR/UKRI grant (COV0170) Humoral Immune Correlates of COVID-19 (HICC), Cambridge Commonwealth, European & International Trust (Cambridge Trust) Topic Categories Vaccines and Immunotherapy (VAC)