Lower T cell response against SARS-CoV-2 variants of concern after mRNA vaccine and risk of breakthrough infections in people with HIV

Abstract

Objectives:We evaluated T-cell immune responses against SARS-CoV-2 variants of concern (VOC) after vaccination in people with HIV (PWH), and their impact on the incidence of disease.Methods:A prospective cohort study. Peripheral blood mononuclear cells (PBMCs) were collected a median of 53 days after second dose of mRNA vaccine. Humoral response and T cell responses against the spike (S) glycoprotein of wild-type SARS-CoV-2 (ancestral Wuhan variant) and mutated S-protein regions found in the Delta and Omicron variants were assessed by flow cytometry analysis.Results:In 142 PWH without preceding SARS-CoV-2 infection, bivariate correlations showed a close association between T-cell responses to the different variants. However, despite at least 70% of PWH having a cellular immune response to any variant, CD4+and CD8+T cell responses against VOC were lower in frequency and magnitude (-3% and -20% for Delta, -33% and -28% for Omicron variant) compared with that observed against the Wuhan strain. A higher magnitude of SARS-CoV-2 spike-specific CD8+T cell responses against all the variants was observed in those PWH with greater immune reconstitution. Notably, 27 symptomatic breakthrough infections (19%) in the setting of Delta and Omicron transmission were observed during follow-up, associated with a significant lower humoral and T-cell response to ancestral strain and VOC. On the contrary, only one PWH with COVID-19 (4%) required hospitalization.Conclusion:A blunted T-cell response against Delta and Omicron variant is observed in PWH who received two doses of mRNA vaccine. This lower immune response is associated with breakthrough SARS-CoV-2 infections.