Alliance for Pandemic Preparedness

February 25, 2021

Evidence of Escape of SARS-CoV-2 Variant B.1.351 from Natural and Vaccine Induced Sera

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Neutralizing antibody titers were lower in assays against the SARS-CoV-2 B.1.351 variant compared to an early isolate from Wuhan across several sample sources. The geometric mean neutralizing titers were lower by 13.3-fold in convalescent plasma from patients infected during the first wave in the UK (n=34), by 3.1-fold in sera from patients infected with the B.1.1.7 variant (n=13), by 7.6-fold in sera from Pfizer vaccine recipients 14-28 days after the 2nd dose (n=25), and by 9-fold in sera from Oxford-AstraZeneca vaccine recipients 4-17 days after the 2nd dose (n=25).

In a panel of 377 monoclonal antibodies (mAbs) raised from convalescent sera of first-wave patients in the UK, 14 out of the 20 of the most potent mAbs had a greater than 10-fold reduction in neutralization titers. In the mAb-based treatments from Regeneron and AstraZeneca, one of the Regeneron mAb pairs (casirivimab) had up to a 773-fold reduction in neutralization titers, while both of the AstraZeneca mAbs had little to no reduction.

Structure-function analysis suggests that the mechanism by which the B.1.351 variant escapes neutralization and provides tighter binding to the angiotensin-converting enzyme-2 (ACE2) receptor to more efficiently enter human cells is primarily driven by the E484K mutation.

Zhou et al. (Feb 17, 2021). Evidence of Escape of SARS-CoV-2 Variant B.1.351 from Natural and Vaccine Induced Sera. Cell. https://doi.org/10.1016/j.cell.2021.02.037