Assessing SARS-CoV-2 immune markers in vaccinated asymptomatic adults after household exposure in Canada (AB-PROTECT): a prospective cohort study.
BACKGROUND Determining the early immune response against SARS-CoV-2 in individuals who are vaccinated is essential for better understanding immune memory and informing COVID-19 vaccine design and use. We aimed to evaluate antibody and T-cell immune markers against SARS-CoV-2 infection among household contacts of index patients infected with SARS-CoV-2. METHODS A prospective observational cohort study was created comprising vaccinated and asymptomatic adult household contacts of outpatients who presented to the Emergency Department or COVID-19 Assessment Centre at Michael Garron Hospital with a SARS-CoV-2 infection in Toronto, ON, Canada. Eligible participants were 18 years or older and had received at least two COVID-19 vaccine doses, amended to three doses after Jan 19, 2022. At enrolment, study staff collected self-reported demographic and clinical data and blood specimens to measure SARS-CoV-2 anti-spike and anti-receptor-binding domain (RBD) IgG and IgA antibodies and conduct SARS-CoV-2 spike-pseudotyped neutralisation assays, live SARS-CoV-2 microneutralisation assays, and assessments of CD4+ and CD8+ T-cell activation and functional cytokine responses to SARS-CoV-2 proteins. Participants were followed up for 28 days with repeat testing for SARS-CoV-2 infection and serological assessments. The primary outcome was SARS-CoV-2 infection within 28 days, identified by virological testing or seroconversion. FINDINGS Between Oct 21, 2021, and Feb 21, 2023, 484 participants were enrolled; of these, for 432 participants (median age 43 years [IQR 38-50]; 217/432 [50%] were female), sufficient follow-up information was available for final analysis. SARS-CoV-2 infection developed in 210 (49%) of 432 participants, of whom 182 (87%) developed symptoms. No change was seen in the probability of infection between the 10th and 90th percentiles of anti-spike IgG levels (1, 95% CI -11 to 14) or anti-RBD IgG levels (1, -11 to 13). The predicted probability decreased by 3% for pseudoneutralisation capacity against ancestral SARS-CoV-2 (95% CI -1 to 14) and by 5% for live-virus microneutralisation titres (-22 to 13). T-cell responses were assessed in a convenience subset of 56 participants starting Jan 19, 2022, of whom 30 (54%) developed SARS-CoV-2 infection. Participants with infection had enhanced Th17 CD4+ T-cell activation responses to SARS-CoV-2 membrane protein stimulation early after household exposure (adjusted odds ratio [OR] 3·58, 95% CI 1·69-8·93). CD4+ and CD8+ T-cell cytokine polyfunctionality was similar between groups. Lower levels of omicron BA.1 spike-stimulated CD8+ T cells only coexpressing GM-CSF and TNF were also seen in participants with infection (adjusted OR 0·52, 95% CI 0·26-0·96). INTERPRETATION Early after household exposure, binding and neutralising antibodies were similar in all participants, but differences in T-cell functional responses were evident in individuals who developed symptoms after SARS-CoV-2 infection. FUNDING COVID-19 Immunity Task Force Initiative Sero-Surveillance and Research Program grant.