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Broadly neutralizing antibodies against sarbecoviruses generated by immunization of macaques with an AS03-adjuvanted COVID-19 vaccine.
Feng, Yupeng; Yuan, Meng; Powers, John M; Hu, Mengyun; Munt, Jennifer E; Arunachalam, Prabhu S; Leist, Sarah R; Bellusci, Lorenza; Kim, JungHyun; Sprouse, Kaitlin R; Adams, Lily E; Sundaramurthy, Sumana; Zhu, Xueyong; Shirreff, Lisa M; Mallory, Michael L; Scobey, Trevor D; Moreno, Alberto; O'Hagan, Derek T; Kleanthous, Harry; Villinger, Francois J; Veesler, David; King, Neil P; Suthar, Mehul S; Khurana, Surender; Baric, Ralph S; Wilson, Ian A; Pulendran, Bali.
  • Feng Y; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA.
  • Yuan M; Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
  • Powers JM; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Hu M; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA.
  • Munt JE; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Arunachalam PS; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA.
  • Leist SR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Bellusci L; Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration (FDA), Silver Spring, MD 20993, USA.
  • Kim J; Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration (FDA), Silver Spring, MD 20993, USA.
  • Sprouse KR; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Adams LE; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Sundaramurthy S; Sino Biological US Inc., Wayne, PA 19087, USA.
  • Zhu X; Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
  • Shirreff LM; New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA 70560, USA.
  • Mallory ML; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Scobey TD; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Moreno A; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • O'Hagan DT; GSK, Rockville, MD 20850, USA.
  • Kleanthous H; Bill and Melinda Gates Foundation, Seattle, WA 98109, USA.
  • Villinger FJ; New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA 70560, USA.
  • Veesler D; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • King NP; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
  • Suthar MS; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Khurana S; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Baric RS; Department of Pediatrics, Emory Vaccine Center, Emory National Primate Research Center, Atlanta, GA 30329, USA.
  • Wilson IA; Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration (FDA), Silver Spring, MD 20993, USA.
  • Pulendran B; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Sci Transl Med ; 15(695): eadg7404, 2023 05 10.
Article in English | MEDLINE | ID: covidwho-2314481
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Severe acute respiratory syndrome-related coronavirus / COVID-19 Type of study: Prognostic study / Randomized controlled trials Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Sci Transl Med Journal subject: Science / Medicine Year: 2023 Document Type: Article Affiliation country: Scitranslmed.adg7404

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Severe acute respiratory syndrome-related coronavirus / COVID-19 Type of study: Prognostic study / Randomized controlled trials Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Sci Transl Med Journal subject: Science / Medicine Year: 2023 Document Type: Article Affiliation country: Scitranslmed.adg7404