4.7 Article

SARS-CoV-2 B.1.617 Mutations L452R and E484Q Are Not Synergistic for Antibody Evasion

Journal

JOURNAL OF INFECTIOUS DISEASES
Volume 224, Issue 6, Pages 989-994

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiab368

Keywords

antibody escape; B.1.617; COVID-19; evasion; fitness; Indian variant; infectivity; neutralizing antibodies; resistance; SARS-CoV-2; spike mutation

Funding

  1. Wellcome Trust [WT108082AIA]
  2. Japanese Agency for Medical Research and Development (AMED) Research Program on Emerging and Re-emerging Infectious Diseases [20fk0108413]
  3. Cambridge NIHR Biomedical Research Centre
  4. Bill and Melinda Gates Foundation via the Phylogenetics And Networks for Generalised Epidemics in Africa (PANGEA) [OPP1175094]
  5. Rosetrees Trust
  6. Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE, a Developing Excellence in Leadership, Training and Science Developing (DELTAS) Africa Initiative [DEL-15-006]

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The SARS-CoV-2 B.1.617 variant from India with key mutations L452R and E484Q shows reduced sensitivity to neutralizing antibodies elicited by the BNT162b2 mRNA vaccine, similar to the effect of L452R or E484Q mutations alone.
The SARS-CoV-2 B.1.617 variant emerged in the Indian state of Maharashtra in late 2020. There have been fears that 2 key mutations seen in the receptor-binding domain, L452R and E484Q, would have additive effects on evasion of neutralizing antibodies. We report that spike bearing L452R and E484Q confers modestly reduced sensitivity to BNT162b2 mRNA vaccine-elicited antibodies following either first or second dose. The effect is similar in magnitude to the loss of sensitivity conferred by L452R or E484Q alone. These data demonstrate reduced sensitivity to vaccine-elicited neutralizing antibodies by L452R and E484Q but lack of synergistic loss of sensitivity.

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