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Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera.

ABSTRACT: SARS-CoV-2 has caused over 2 million deaths in little over a year. Vaccines are being deployed at scale, aiming to generate responses against the virus spike. The scale of the pandemic and error-prone virus replication is leading to the appearance of mutant viruses and potentially escape from antibody responses. Variant B.1.1.7, now dominant in the UK, with increased transmission, harbors 9 amino acid changes in the spike, including N501Y in the ACE2 interacting surface. We examine the ability of B.1.1.7 to evade antibody responses elicited by natural SARS-CoV-2 infection or vaccination. We map the impact of N501Y by structure/function analysis of a large panel of well-characterized monoclonal antibodies. B.1.1.7 is harder to neutralize than parental virus, compromising neutralization by some members of a major class of public antibodies through light-chain contacts with residue 501. However, widespread escape from monoclonal antibodies or antibody responses generated by natural infection or vaccination was not observed.

SUBMITTER: Supasa P

PROVIDER: S-EPMC7891044 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera.

Supasa Piyada P Zhou Daming D Dejnirattisai Wanwisa W Liu Chang C Mentzer Alexander J AJ Ginn Helen M HM Zhao Yuguang Y Duyvesteyn Helen M E HME Nutalai Rungtiwa R Tuekprakhon Aekkachai A Wang Beibei B Paesen Guido C GC Slon-Campos Jose J López-Camacho César C Hallis Bassam B Coombes Naomi N Bewley Kevin R KR Charlton Sue S Walter Thomas S TS Barnes Eleanor E Dunachie Susanna J SJ Skelly Donal D Lumley Sheila F SF Baker Natalie N Shaik Imam I Humphries Holly E HE Godwin Kerry K Gent Nick N Sienkiewicz Alex A Dold Christina C Levin Robert R Dong Tao T Pollard Andrew J AJ Knight Julian C JC Klenerman Paul P Crook Derrick D Lambe Teresa T Clutterbuck Elizabeth E Bibi Sagida S Flaxman Amy A Bittaye Mustapha M Belij-Rammerstorfer Sandra S Gilbert Sarah S Hall David R DR Williams Mark A MA Paterson Neil G NG James William W Carroll Miles W MW Fry Elizabeth E EE Mongkolsapaya Juthathip J Ren Jingshan J Stuart David I DI Screaton Gavin R GR

Cell 20210218 8

SARS-CoV-2 has caused over 2 million deaths in little over a year. Vaccines are being deployed at scale, aiming to generate responses against the virus spike. The scale of the pandemic and error-prone virus replication is leading to the appearance of mutant viruses and potentially escape from antibody responses. Variant B.1.1.7, now dominant in the UK, with increased transmission, harbors 9 amino acid changes in the spike, including N501Y in the ACE2 interacting surface. We examine the ability o ...[more]

PMID: 33743891

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Project description:The increasing prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with spike protein mutations raises concerns that antibodies elicited by natural infection or vaccination and therapeutic monoclonal antibodies will become less effective. We show that convalescent-phase sera neutralize pseudotyped viruses with the B.1.1.7, B.1.351, B.1.1.248, COH.20G/677H, 20A.EU2, and mink cluster 5 spike proteins with only a minor loss in titer. Similarly, antibodies elicited by Pfizer BNT162b2 vaccination neutralized B.1.351 and B.1.1.248 with only a 3-fold decrease in titer, an effect attributable to E484K. Analysis of the Regeneron monoclonal antibodies REGN10933 and REGN10987 showed that REGN10933 has lost neutralizing activity against the B.1.351 and B.1.1.248 pseudotyped viruses, and the cocktail is 9- to 15-fold decreased in titer. These findings suggest that antibodies elicited by natural infection and by the Pfizer vaccine will maintain protection against the B.1.1.7, B.1.351, and B.1.1.248 variants but that monoclonal antibody therapy may be less effective for patients infected with B.1.351 or B.1.1.248 SARS-CoV-2. IMPORTANCE The rapid evolution of SARS-CoV-2 variants has raised concerns with regard to their potential to escape from vaccine-elicited antibodies and anti-spike protein monoclonal antibodies. We report here on an analysis of sera from recovered patients and vaccinated individuals and on neutralization by Regeneron therapeutic monoclonal antibodies. Overall, the variants were neutralized nearly as well as the wild-type pseudotyped virus. The B.1.351 variant was somewhat resistant to vaccine-elicited antibodies but was still readily neutralized. One of the two Regeneron therapeutic monoclonal antibodies seems to have lost most of its activity against the B.1.351 variant, raising concerns that the combination therapy might be less effective for some patients. The findings should alleviate concerns that vaccines will become ineffective but suggest the importance of continued surveillance for potential new variants.

Dataset Information

Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera.

Publications

Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera.

Similar Datasets

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