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Broad SARS-CoV-2 neutralization by monoclonal and bispecific antibodies derived from a Gamma-infected individual

Journal Article · · iScience
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  1. University of Amsterdam (The Netherlands); Amsterdam Institute for Infection and Immunity, Infectious Diseases (The Netherlands)
  2. The Scripps Research Institute, La Jolla, CA (United States)
  3. National Institute for Public Health and the Environment (RIVM), Bilthoven (The Netherlands)
  4. University of Amsterdam (The Netherlands); Amsterdam Institute for Infection and Immunity, Infectious Diseases (The Netherlands); National Institute for Public Health and the Environment (RIVM), Bilthoven (The Netherlands)
  5. Amsterdam Institute for Infection and Immunity, Infectious Diseases (The Netherlands); University of Amsterdam (The Netherlands)
  6. University of Amsterdam (The Netherlands); Amsterdam Institute for Infection and Immunity, Infectious Diseases (The Netherlands); Cornell University, New York, NY (United States)
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has remained a medical threat due to the evolution of multiple variants that acquire resistance to vaccines and prior infection. Therefore, it is imperative to discover monoclonal antibodies (mAbs) that neutralize a broad range of SARS-CoV-2 variants. A stabilized spike glycoprotein was used to enrich antigen-specific B cells from an individual with a primary Gamma variant infection. Five mAbs selected from those B cells showed considerable neutralizing potency against multiple variants, with COVA309-35 being the most potent against the autologous virus, as well as Omicron BA.1 and BA.2, and COVA309-22 having binding and neutralization activity against Omicron BA.4/5, BQ.1.1, and XBB.1. When combining the COVA309 mAbs as cocktails or bispecific antibodies, the breadth and potency were improved. In addition, the mechanism of cross-neutralization of the COVA309 mAbs was elucidated by structural analysis. Altogether these data indicate that a Gamma-infected individual can develop broadly neutralizing antibodies.
Research Organization:
SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02-76SF00515
OSTI ID:
2469865
Journal Information:
iScience, Journal Name: iScience Journal Issue: 10 Vol. 26; ISSN 2589-0042
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English

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