mRNA-1273 SARS-CoV-2 vaccination in people with HIV: an immune correlates analysis of CD4+ T cell responses in the multicenter CoVPN 3008 observational study

Abstract

T cell correlates of COVID-19 risk are poorly defined, particularly in people with HIV (PWH). CoVPN 3008 (NCT05168813) Part A was a prospective 14,002-participant cohort study that administered one or two doses of mRNA-1273 COVID-19 vaccine, depending on baseline SARS-CoV-2 serostatus, in participants (83% PWH) in sub-Saharan Africa. Participants self-monitored for prespecified COVID-19 symptoms, defined by Centers for Disease Control and Prevention symptom criteria. Previous work showed that protection from COVID-19 was superior for hybrid versus vaccine-induced immunity, and that neutralizing antibody titers inversely associated with COVID-19 risk. In the present work, we measured T cell responses to Spike and Nucleocapsid at baseline and 4 weeks post last-vaccination (Peak) in a case-cohort study and assessed them as correlates of risk. In Hybrid Group PWH (n = 22 cases), COVID-19 risk over 6 months decreased with increasing Peak Spike BA.4/5-specific CD4 + T cell responses, from 15.8%, 4.7%, and 0% risk at 0.1%, 0.2%, and 0.3% IFN-γ and/or IL-2 response magnitude, respectively. Including baseline Spike-specific neutralizing antibody titer and Peak CD4 + T cell functionality score in the same model increased the association’s strength (overall p < 0.001). Thus, CD4 + T cell responses are an independent correlate of COVID-19 risk among PWH with pre-existing SARS-CoV-2 immunity.

Bo Zhang

Assistant Professor of Biostatistics

My research interests include design of observational studies, instrumental variables, application of causal inference in medicine and applied statistics in general.