دورية أكاديمية
أعرض في EDS

Neutralizing antibodies protect mice against Venezuelan equine encephalitis virus aerosol challenge.

التفاصيل البيبلوغرافية
العنوان: Neutralizing antibodies protect mice against Venezuelan equine encephalitis virus aerosol challenge.
المؤلفون: Kafai NM; Department of Medicine, Washington University School of Medicine, St. Louis, MO.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO., Williamson LE; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN.; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN., Binshtein E; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN., Sukupolvi-Petty S; Department of Medicine, Washington University School of Medicine, St. Louis, MO., Gardner CL; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA.; Department of Immunology, University of Pittsburgh, Pittsburgh, PA.; United States Army Research Institute for Infectious Diseases, Fort Detrick, MD., Liu J; Department of Medicine, Washington University School of Medicine, St. Louis, MO., Mackin S; Department of Medicine, Washington University School of Medicine, St. Louis, MO.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO., Kim AS; Department of Medicine, Washington University School of Medicine, St. Louis, MO.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO., Kose N; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN., Carnahan RH; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN.; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN., Jung A; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO., Droit L; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO., Reed DS; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA.; Department of Immunology, University of Pittsburgh, Pittsburgh, PA., Handley SA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO., Klimstra WB; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA.; Department of Immunology, University of Pittsburgh, Pittsburgh, PA., Crowe JE; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN.; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN.; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN., Diamond MS; Department of Medicine, Washington University School of Medicine, St. Louis, MO.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO.; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO.
المصدر: The Journal of experimental medicine [J Exp Med] 2022 Apr 04; Vol. 219 (4). Date of Electronic Publication: 2022 Mar 17.
نوع المنشور: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 2985109R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-9538 (Electronic) Linking ISSN: 00221007 NLM ISO Abbreviation: J Exp Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Rockefeller University Press
مواضيع طبية MeSH: Encephalitis Virus, Venezuelan Equine* , Encephalomyelitis, Venezuelan Equine*/prevention & control , Viral Vaccines*, Aerosols ; Animals ; Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; Cryoelectron Microscopy ; Horses ; Mice
مستخلص: Venezuelan equine encephalitis virus (VEEV) remains a risk for epidemic emergence or use as an aerosolized bioweapon. To develop possible countermeasures, we isolated VEEV-specific neutralizing monoclonal antibodies (mAbs) from mice and a human immunized with attenuated VEEV strains. Functional assays and epitope mapping established that potently inhibitory anti-VEEV mAbs bind distinct antigenic sites in the A or B domains of the E2 glycoprotein and block multiple steps in the viral replication cycle including attachment, fusion, and egress. A 3.2-Å cryo-electron microscopy reconstruction of VEEV virus-like particles bound by a human Fab suggests that antibody engagement of the B domain may result in cross-linking of neighboring spikes to prevent conformational requirements for viral fusion. Prophylaxis or postexposure therapy with these mAbs protected mice against lethal aerosol challenge with VEEV. Our study defines functional and structural mechanisms of mAb protection and suggests that multiple antigenic determinants on VEEV can be targeted for vaccine or antibody-based therapeutic development.
Competing Interests: Disclosures: M.S. Diamond is a consultant for Inbios, Vir Biotechnology, and Carnival Corporation, and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. Washington University has licensed murine anti-VEEV mAbs, and M.S. Diamond, S. Sukupolvi-Petty, and N.M. Kafai are inventors. J.E. Crowe has served as a consultant for Luna Biologics, is a member of the Scientific Advisory Boards of Meissa Vaccines, and is founder of IDBiologics. The Crowe laboratory has received unrelated sponsored research agreements from Takeda, AstraZeneca, and IDBiologics. J.E. Crowe reported grants from NIH during the conduct of the study and from GSK and Merck and grants from IDBiologics outside the submitted work; in addition, J. Crowe had a patent app for human antibodies for VEEV pending. The Klimstra laboratory has received unrelated research support from SAB Biotherapeutics and Tiba Biotechnology. The other authors have no additional conflicts of interest to declare. No other disclosures were reported.
(© 2022 Kafai et al.)
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معلومات مُعتمدة: R01 AI164653 United States AI NIAID NIH HHS; U24 GM129541 United States GM NIGMS NIH HHS; R01 AI095436 United States AI NIAID NIH HHS; U01 AI151810 United States AI NIAID NIH HHS; U19 AI142790 United States AI NIAID NIH HHS; T32 AI007172 United States AI NIAID NIH HHS; T32 HL069765 United States HL NHLBI NIH HHS; F31 AI145189 United States AI NIAID NIH HHS; R01 AI095436 United States NH NIH HHS; R01 AI153209 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (Aerosols)
0 (Antibodies, Monoclonal)
0 (Antibodies, Neutralizing)
0 (Antibodies, Viral)
0 (Viral Vaccines)
تواريخ الأحداث: Date Created: 20220317 Date Completed: 20220415 Latest Revision: 20240923
رمز التحديث: 20240923
مُعرف محوري في PubMed: PMC9195047
DOI: 10.1084/jem.20212532
PMID: 35297953
قاعدة البيانات: MEDLINE
الوصف
تدمد:1540-9538
DOI:10.1084/jem.20212532