Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals

TLDR

BNT162b2 is highly effective against SARS‑CoV‑2, yet variants of concern may evade protection because vaccine sera neutralize B.1.1.7 and B.1.351 less efficiently in vitro. The authors conducted a matched cohort study to assess whether vaccine effectiveness against VOCs is reduced by comparing the proportion of these variants in breakthrough infections versus unvaccinated controls. They sequenced 813 nasopharyngeal swabs from Clalit Health Services patients, matching cases and controls to evaluate variant distribution. The study found that B.1.351 predominated among breakthrough cases ≥7 days after the second dose and B.1.1.7 among cases 2 weeks after the first dose to 6 days after the second, indicating reduced vaccine effectiveness in those windows and highlighting the need for variant surveillance and higher vaccination coverage.

Abstract

The BNT162b2 mRNA vaccine is highly effective against SARS-CoV-2. However, apprehension exists that variants of concern (VOCs) may evade vaccine protection, due to evidence of reduced neutralization of the VOCs B.1.1.7 and B.1.351 by vaccine sera in laboratory assays. We performed a matched cohort study to examine the distribution of VOCs in infections of BNT162b2 mRNA vaccinees from Clalit Health Services (Israel) using viral genomic sequencing, and hypothesized that if vaccine effectiveness against a VOC is reduced, its proportion among breakthrough cases would be higher than in unvaccinated controls. Analyzing 813 viral genome sequences from nasopharyngeal swabs, we showed that vaccinees who tested positive at least 7 days after the second dose were disproportionally infected with B.1.351, compared with controls. Those who tested positive between 2 weeks after the first dose and 6 days after the second dose were disproportionally infected by B.1.1.7. These findings suggest reduced vaccine effectiveness against both VOCs within particular time windows. Our results emphasize the importance of rigorously tracking viral variants, and of increasing vaccination to prevent the spread of VOCs.