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SARS-CoV-2 B.1.1.7 sensitivity to mRNA vaccine-elicited, convalescent and monoclonal antibodies.

ABSTRACT: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) transmission is uncontrolled in many parts of the world, compounded in some areas by higher transmission potential of the B1.1.7 variant now seen in 50 countries. It is unclear whether responses to SARS-CoV-2 vaccines based on the prototypic strain will be impacted by mutations found in B.1.1.7. Here we assessed immune responses following vaccination with mRNA-based vaccine BNT162b2. We measured neutralising antibody responses following a single immunization using pseudoviruses expressing the wild-type Spike protein or the 8 amino acid mutations found in the B.1.1.7 spike protein. The vaccine sera exhibited a broad range of neutralising titres against the wild-type pseudoviruses that were modestly reduced against B.1.1.7 variant. This reduction was also evident in sera from some convalescent patients. Decreased B.1.1.7 neutralisation was also observed with monoclonal antibodies targeting the N-terminal domain (9 out of 10), the Receptor Binding Motif (RBM) (5 out of 31), but not in neutralising mAbs binding outside the RBM. Introduction of the E484K mutation in a B.1.1.7 background to reflect newly emerging viruses in the UK led to a more substantial loss of neutralising activity by vaccine-elicited antibodies and mAbs (19 out of 31) over that conferred by the B.1.1.7 mutations alone. E484K emergence on a B.1.1.7 background represents a threat to the vaccine BNT162b.

SUBMITTER: Collier DA

PROVIDER: S-EPMC7899479 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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SARS-CoV-2 B.1.1.7 sensitivity to mRNA vaccine-elicited, convalescent and monoclonal antibodies.

Collier Dami A DA De Marco Anna A Ferreira Isabella A T M IATM Meng Bo B Datir Rawlings R Walls Alexandra C AC Kemp S Steven A SA Bassi Jessica J Pinto Dora D Fregni Chiara Silacci CS Bianchi Siro S Tortorici M Alejandra MA Bowen John J Culap Katja K Jaconi Stefano S Cameroni Elisabetta E Snell Gyorgy G Pizzuto Matteo S MS Pellanda Alessandra Franzetti AF Garzoni Christian C Riva Agostino A Elmer Anne A Kingston Nathalie N Graves Barbara B McCoy Laura E LE Smith Kenneth Gc KG Bradley John R JR Temperton Nigel N Ceron-Gutierrez L Lourdes L Barcenas-Morales Gabriela G Harvey William W Virgin Herbert W HW Lanzavecchia Antonio A Piccoli Luca L Doffinger Rainer R Wills Mark M Veesler David D Corti Davide D Gupta Ravindra K RK

medRxiv : the preprint server for health sciences 20210215

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) transmission is uncontrolled in many parts of the world, compounded in some areas by higher transmission potential of the B1.1.7 variant now seen in 50 countries. It is unclear whether responses to SARS-CoV-2 vaccines based on the prototypic strain will be impacted by mutations found in B.1.1.7. Here we assessed immune responses following vaccination with mRNA-based vaccine BNT162b2. We measured neutralising antibody responses followin ...[more]

PMID: 33619509

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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

SARS-CoV-2 B.1.1.7 sensitivity to mRNA vaccine-elicited, convalescent and monoclonal antibodies.

Publications

SARS-CoV-2 B.1.1.7 sensitivity to mRNA vaccine-elicited, convalescent and monoclonal antibodies.

Similar Datasets

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