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Background Despite high vaccine coverage, an increase in breakthrough coronavirus disease 2019 (COVID-19) infections, prompted administration of a third BNT162b2 dose to people aged >60 years in Israel since July 2021. Here, we report real-world immunogenicity following third dose. Methods Overall, 208 healthcare workers aged >60 years were included. Paired pre– and post–second and/or third dose immunoglobulin G (IgG) and neutralizing antibody titers were compared. A subpopulation of low responders to the second dose was also tested for T-cell activation. For 25 paired serum samples, we tested neutralization of wild-type vs neutralization of Delta and Lambda variants, pre– and post–third dose. Active surveillance of vaccine adverse events was conducted through surveys. Results A pronounced immune response was observed following the third dose, including a 33-fold and 51-fold increase in IgG and neutralizing antibody, respectively. The neutralizing antibody levels post–third dose were 9.34 times higher than post–second dose (geometric mean titer, 2598 [95% confidence interval {CI}, 2085–3237] vs 207 [95% CI, 126–339]). Nine previously low responders had a significant antibody increase post–third dose, and 7 of 9 showed increase in T-cell activation. Additionally, sera obtained post–third dose highly and comparably neutralized the wild-type and Delta and Lambda variants. Of 1056 responders to the adverse-event survey, none had serious events. Conclusions We demonstrate a rapid and broad immune response to the third BNT162b2 dose in individuals >60 years of age.

Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may influence the effectiveness of existing laboratory diagnostics. In the current study we determined whether the British (20I/501Y.V1) and South African (20H/501Y.V2) SARS-CoV-2 variants of concern are detected with an in-house S1-based antigen detection assay, analyzing spiked pools of quantitative reverse-transcription polymerase chain reaction–negative nasopharyngeal swab specimens. The assay, combining 4 monoclonal antibodies, allowed sensitive detection of both the wild type and the variants of concern, despite accumulation of several mutations in the variants’ S1 region—results suggesting that this combination, targeting distinct epitopes, enables both specificity and the universality.