Spike-antibody responses following first and second doses of ChAdOx1 and BNT162b2 vaccines by age, gender, and clinical factors - a prospective community cohort study (Virus Watch)

Background Vaccination constitutes the best long-term solution against Coronavirus Disease 2019 (COVID-19). Real-world immunogenicity data are sparse, particularly for ChAdOx1 and in populations with chronic conditions; and given the extended dosing interval in the UK, it is also important to understand antibody responses in SARS-CoV-2-naive individuals following a single dose. Methods Adults aged 18+ years from households enrolled in Virus Watch, a prospective community cohort study in England and Wales, provided capillary blood samples and self-reported vaccination status. Primary outcome variables were quantitative Spike total antibody levels (U/ml) and seropositivity to Spike (>=0.8 U/ml), as per the Roche Elecsys Anti-SARS-CoV-2 S assay. Samples seropositive for Nucleocapsid, and samples taken prior to vaccination, were excluded. Outcomes were analysed by days since vaccination, vaccine type (BNT162b2 and ChAdOx1), and a range of self-reported demographic and clinical factors. Results 8,517 vaccinated participants (median age 65 years [IQR: 58, 71]), contributed 13,232 samples (8,115 following ChAdOx1, 5,008 following BNT162b2). Seropositivity to Spike was 96.42% (95%CI 96, 96.79) at 28-34 days following a single dose, reaching 99.08% (97.8, 99.62) at 7-14 days after a second dose. Seropositivity rates, and Spike-antibody levels rose more quickly following the first dose of BNT162b2, however, were equivalent for both vaccines by 4 and 8 weeks, respectively. There was evidence of lower S-antibody levels with increasing age (p=0.0001). In partially vaccinated 65-79 year-olds, lower S-antibody levels were observed in men (25.9 vs 42.3 U/ml, p =250U/ml) were observed for nearly all individuals. Interpretation A single dose of either BNT162b2 or ChAdOx1 leads to high Spike seropositivity rates in SARS-CoV-2-naive individuals. However, observed disparities in antibody levels after the first dose by vaccine type, age, and comorbidities highlight the importance of ongoing non-pharmaceutical preventative measures such as social distancing, for partially vaccinated adults, particularly those who are older and more clinically vulnerable.