Neutralizing antibody activity against 21 SARS-CoV-2 variants in older adults vaccinated with BNT162b2

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.

Immunogenicity and reactogenicity of mRNA COVID-19 vaccine booster administered by intradermal or intramuscular route in Thai Older adults

“…We observed marginally lower neutralizing antibodies and cellular immune responses among adults aged ≥80 years compared with adults aged 65-79 years. This is consistent with previous studies of BNT162b2 that found lower neutralizing antibody responses in older adults compared with younger adults [16,17]. This underscores the importance of choice of vaccine in older adults.…”

Utilization of the Abbott SARS-CoV-2 IgG II Quant Assay To Identify High-Titer Anti-SARS-CoV-2 Neutralizing Plasma against Wild-Type and Variant SARS-CoV-2 Viruses

“…There are a variety of neutralization assays that have been described to be able to measure functional antibody neutralization against wild-type as well as variant SARS-CoV-2 that involve binding proxy assays ( 24 – 27 ), pseudovirus, or VLP neutralization ( 7 , 25 , 26 ) as well as SARS-CoV-2 culture-based neutralization ( 26 , 28 ). Not all methods compare wild-type or variant SARS-CoV-2 neutralization.…”

Comparative Analysis of Antibody Titers against the Spike Protein of SARS-CoV-2 Variants in Infected Patient Cohorts and Diverse Vaccination Regimes

“…The beta variant was the most neutralization- and vaccine-resistant of the first four variants of concern, including the delta strain [ 45 ]. In contrast, Newman et al observed no neutralizing capacity against the beta variant of SARS-CoV-2 in sera of elderly people vaccinated twice with BT [ 46 ]. The differences in neutralization potential of α-Spike-Ab between the studies might be explained on the one hand by the presence of younger participants in our study, and on the other, by a third inoculation with the mRNA vaccine after six months.…”