The Lancet. Microbe · 2026
Assessing SARS-CoV-2 immune markers in vaccinated asymptomatic adults after household exposure in Canada (AB-PROTECT): a prospective cohort study.
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Kandel Christopher, Breznik Jessica A, Taylor Maureen, Colwill Karen, Hu Queenie, Llanes Andrea, Crowl Gloria, Elliott Helen Deborah, Shi Gavin, Li Xinliu Angel, Lefebvre Maxime, Lee Yaejin, Kurtesi Alexandra, Qi Freda, Delgado-Brand Melanie, Tursun Tulunay R, Mailhot Geneviève, Tersigni Martina, Wu Ying, Ang Jann C, Kozak Rob, Cowbrough Braeden, Benoit Jenna M, McCready Janine, Powis Jeff, Verschoor Chris P, Bramson Jonathan L, Miller Matthew S, Bowdish Dawn M E, Gingras Anne-Claude, McGeer Allison
Аннотация
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.
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.