Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques.

Autor:	Edwards CT; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Karunakaran KA; Department of Pathology, Microbiology & Immunology, Vanderbilt University, Nashville, TN 37235, USA., Garcia E; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; Mayo Clinic Medical Scientist Training Program, Mayo Clinic College of Medicine and Science, 200 First Street SW, Rochester, Minnesota 55356, USA., Beutler N; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA., Gagne M; Vaccine Research Center; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Golden N; Tulane National Primate Research Center, Covington, LA, USA., Aoued H; Emory National Primate Research Center Genomics Core, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Pellegrini KL; Emory National Primate Research Center Genomics Core, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Burnett MR; Vaccine Research Center; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Honeycutt CC; Vaccine Research Center; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Lapp SA; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Ton T; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Lin MC; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Metz A; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Bombin A; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Goff K; Tulane National Primate Research Center, Covington, LA, USA., Scheuermann SE; Tulane National Primate Research Center, Covington, LA, USA., Wilkes A; Division of Animal Resources, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Wood JS; Division of Animal Resources, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Ehnert S; Division of Animal Resources, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Weissman S; Division of Animal Resources, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Curran EH; Division of Pathology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Roy M; Division of Pathology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Dessasau E; Division of Histology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Paiardini M; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Emory Vaccine Center, Emory National Primate Research Center, Atlanta, Georgia, USA.; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA., Upadhyay AA; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Moore I; Division of Pathology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA., Maness NJ; Tulane National Primate Research Center, Covington, LA, USA., Douek DC; Vaccine Research Center; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Piantadosi A; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.; Emory Vaccine Center, Emory National Primate Research Center, Atlanta, Georgia, USA.; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA., Andrabi R; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA., Rogers TR; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA., Burton DR; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA., Bosinger SE; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Emory Vaccine Center, Emory National Primate Research Center, Atlanta, Georgia, USA.; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Jul 30. Date of Electronic Publication: 2024 Jul 30.
DOI:	10.1101/2024.07.30.605768
Abstrakt:	The continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other β-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines. One of these S2-directed mAbs, CC40.8, has demonstrated protective efficacy in small animal models against SARS-CoV-2 challenge. As the next step in the pre-clinical testing of S2-directed antibodies as a strategy to protect from SARS-CoV-2 infection, we evaluated the in vivo efficacy of CC40.8 in a clinically relevant non-human primate model by conducting passive antibody transfer to rhesus macaques (RM) followed by SARS-CoV-2 challenge. CC40.8 mAb was intravenously infused at 10mg/kg, 1mg/kg, or 0.1 mg/kg into groups (n=6) of RM, alongside one group that received a control antibody (PGT121). Viral loads in the lower airway were significantly reduced in animals receiving higher doses of CC40.8. We observed a significant reduction in inflammatory cytokines and macrophages within the lower airway of animals infused with 10mg/kg and 1mg/kg doses of CC40.8. Viral genome sequencing demonstrated a lack of escape mutations in the CC40.8 epitope. Collectively, these data demonstrate the protective efficiency of broadly neutralizing S2-targeting antibodies against SARS-CoV-2 infection within the lower airway while providing critical preclinical work necessary for the development of pan-β-CoV vaccines. Competing Interests: Conflicting Interests: RA, TFR, and DRB are listed as inventors on pending patent applications describing the SARS-CoV-2 and HCoV-HKU1 S cross-reactive antibodies. DRB and RA are listed as inventors on a pending patent application describing the S2 stem epitope immunogens identified in this study. DRB is a consultant for IAVI. All other authors declare that they have no competing interests.
Databáze:	MEDLINE
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