Abstract
SARS-CoV-2 variants may threaten the effectiveness of vaccines and antivirals to mitigate serious COVID-19 disease. This is of most concern in clinically vulnerable groups such as older adults. We analysed 72 sera samples from 37 individuals, aged 70-89 years, vaccinated with two doses of BNT162b2 (Pfizer-BioNTech) 3 weeks apart, for neutralizing antibody responses to wildtype SARS-CoV-2. Between 3 and 20 weeks after the second vaccine dose, neutralizing antibody titres fell 4.9-fold to a median titre of 21.3 (neutralization dose 80%), with 21.6% of individuals having no detectable neutralizing antibodies at the later time point. Next, we examined neutralization of 21 distinct SARS-CoV-2 variant spike proteins with these sera, and confirmed substantial antigenic escape, especially for the Omicron (B.1.1.529, BA.1/BA.2), Beta (B.1.351), Delta (B.1.617.2), Theta (P.3), C.1.2 and B.1.638 spike variants. By combining pseudotype neutralization with specific receptor-binding domain (RBD) enzyme-linked immunosorbent assays, we showed that changes to position 484 in the spike RBD were mainly responsible for SARS-CoV-2 neutralizing antibody escape. Nineteen sera from the same individuals boosted with a third dose of BNT162b2 contained higher neutralizing antibody titres, providing cross-protection against Omicron BA.1 and BA.2. Despite SARS-CoV-2 immunity waning over time in older adults, booster vaccines can elicit broad neutralizing antibodies against a large number of SARS-CoV-2 variants in this clinically vulnerable cohort.
【초록키워드】 neutralizing antibody, SARS-CoV-2, Vaccine, cross-protection, Antiviral, Older adults, Neutralizing antibodies, B.1.351, neutralization, variant, SARS-CoV-2 variant, Delta, B.1.617.2, omicron, variants, SARS-CoV-2 immunity, Spike protein, COVID-19 disease, vaccine dose, BNT162b2, Adults, Cohort, Antibody responses, SARS-CoV-2 variants, RBD, enzyme-linked immunosorbent assays, pseudotype, sera, Effectiveness, Beta, spike variants, B.1.1.529, group, disease, change, Pfizer-BioNTech, Neutralizing antibody response, SARS-CoV-2 neutralizing antibody, booster vaccines, Booster vaccine, dose, Spike proteins, Older, enzyme, individual, antigenic, domain, serious COVID-19, titre, neutralizing antibody responses, wildtype, neutralizing antibody titres, mitigate, responsible, examined, detectable, clinically, analysed, median, elicit, individuals, neutralizing antibody titre, of BNT162b2, 【제목키워드】 antibody, SARS-CoV-2 variant, Older,