Highlights d Pfizer-BTN162b2 vaccine heightens neutralization potency compared to convalescent sera d BTN162b2 shows similar neutralization against WT SARS-CoV-2 and its B.1.1.7 variant d BTN162b2 displays a 6.8-fold reduction in neutralization against the B.1.351 variant d N501Y and E484K/K417N S mutations enhance viral infectivity and neutralization resistance

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Towards eradicating COVID19, developing vaccines that induce high levels of neutralizing antibodies is a main goal. As counter measurements, viral escape mutants rapidly emerge and potentially compromise vaccine efficiency. Herein we monitored ability of convalescent or Pfizer-BTN162b2 post-vaccination sera to neutralize wide-type SARS- CoV2 or its UK-B.1.1.7 and SA-B.1.351 variants. Relative to convalescent sera, post- vaccination sera exhibited higher levels of neutralizing antibodies against wild-type or mutated viruses. However, while SARS-CoV2 wild-type and UK-N501Y were similarly neutralized by tested sera, the SA-N501Y/K417N/E484K variant moderately escaped neutralization. Significant contribution to infectivity and sensitivity to neutralization was attributed to each of the variants and their single or combined mutations, highlighting alternative mechanisms by which prevalent variants with either N501Y or E484K/K417N mutations spread. Our study validates the clinical significance of currently administered vaccines, but emphasizes that their efficacy may be compromised by circulated variants, urging the development of new ones with broader neutralization functions.