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Title: Broadly neutralizing antibodies against sarbecoviruses generated by immunization of macaques with an AS03-adjuvanted COVID-19 vaccine

Journal Article · · Science Translational Medicine
ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [3]; ORCiD logo [1];  [3]; ORCiD logo [1]; ORCiD logo [3]; ORCiD logo [4]; ORCiD logo [4]; ORCiD logo [5]; ORCiD logo [3]; ORCiD logo [6]; ORCiD logo [2]; ORCiD logo [7]; ORCiD logo [3];  [3]; ORCiD logo [8];  [9];  [10]; ORCiD logo [7] more »; ORCiD logo [11]; ORCiD logo [5]; ORCiD logo [12]; ORCiD logo [4]; ORCiD logo [3]; ORCiD logo [2]; ORCiD logo [13] « less
  1. Stanford Univ., CA (United States)
  2. Scripps Research Institute, La Jolla, CA (United States)
  3. University of North Carolina, Chapel Hill, NC (United States)
  4. U.S. Food and Drug Administration (FDA), Silver Spring, MD (United States). Center for Biologics Evaluation and Research
  5. Univ. of Washington, Seattle, WA (United States)
  6. Sino Biological US, Inc. Wayne, PA (United States)
  7. Univ. of Louisiana at Lafayette, New Iberia, LA (United States)
  8. Emory Univ., Atlanta, GA (United States). School of Medicine
  9. GSK, Rockville, MD (United States)
  10. Bill and Melinda Gates Foundation, Seattle, WA (United States)
  11. Univ. of Washington, Seattle, WA (United States). Howard Hughes Medical Institute
  12. Emory National Primate Research Center, Atlanta, GA (United States)
  13. Stanford Univ., CA (United States). School of Medicine

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has placed an imperative on the development of countermeasures that provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent monoclonal antibodies (mAbs) that neutralized multiple sarbecoviruses from macaques vaccinated with AS03-adjuvanted monovalent subunit vaccines. Longitudinal analysis revealed progressive accumulation of somatic mutation in the immunoglobulin genes of antigen-specific memory B cells (MBCs) for at least 1 year after primary vaccination. Antibodies generated from these antigen-specific MBCs at 5 to 12 months after vaccination displayed greater potency and breadth relative to those identified at 1.4 months. Fifteen of the 338 (about 4.4%) antibodies isolated at 1.4 to 6 months after the primary vaccination showed potency against SARS-CoV-2 BA.1, despite the absence of serum BA.1 neutralization. 25F9 and 20A7 neutralized authentic clade 1 sarbecoviruses (SARS-CoV, WIV-1, SHC014, SARS-CoV-2 D614G, BA.1, and Pangolin-GD) and vesicular stomatitis virus–pseudotyped clade 3 sarbecoviruses (BtKY72 and PRD-0038). 20A7 and 27A12 showed potent neutralization against all SARS-CoV-2 variants and multiple Omicron sublineages, including BA.1, BA.2, BA.3, BA.4/5, BQ.1, BQ.1.1, and XBB. Crystallography studies revealed the molecular basis of broad and potent neutralization through targeting conserved sites within the RBD. Prophylactic protection of 25F9, 20A7, and 27A12 was confirmed in mice, and administration of 25F9 particularly provided complete protection against SARS-CoV-2, BA.1, SARS-CoV, and SHC014 challenge. These data underscore the extremely potent and broad activity of these mAbs against sarbecoviruses.

Research Organization:
SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL); Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF); Bill and Melinda Gates Foundation; National Institute of Allergy and Infectious Diseases (NIAID); U.S. Food and Drug Administration (FDA); National Cancer Institute (NCI); National Institute of General Medical Sciences (NIGMS); USDOE Office of Science (SC), Biological and Environmental Research (BER)
Grant/Contract Number:
AC02-76SF00515; AC02-06CH11357; INV-018675; INV-004923; INV-010680; OPP1156262; DP1AI158186; 75N93022C00036; P01AI167966; OCET 2021-1565; ACB-12002; AGM-12006; P30GM138396; P30GM133894; 5P30CA016086-41
OSTI ID:
1989359
Journal Information:
Science Translational Medicine, Vol. 15, Issue 695; ISSN 1946-6234
Publisher:
AAASCopyright Statement
Country of Publication:
United States
Language:
English

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