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Therapeutic alphavirus cross-reactive E1 human antibodies inhibit viral egress.
Williamson, Lauren E; Reeder, Kristen M; Bailey, Kevin; Tran, Minh H; Roy, Vicky; Fouch, Mallorie E; Kose, Nurgun; Trivette, Andrew; Nargi, Rachel S; Winkler, Emma S; Kim, Arthur S; Gainza, Christopher; Rodriguez, Jessica; Armstrong, Erica; Sutton, Rachel E; Reidy, Joseph; Carnahan, Robert H; McDonald, W Hayes; Schoeder, Clara T; Klimstra, William B; Davidson, Edgar; Doranz, Benjamin J; Alter, Galit; Meiler, Jens; Schey, Kevin L; Julander, Justin G; Diamond, Michael S; Crowe, James E.
Afiliación
  • Williamson LE; Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232, USA; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Reeder KM; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Bailey K; Institute for Antiviral Research, Utah State University, Logan, UT 84335, USA.
  • Tran MH; Chemical and Physical Biology Program, Vanderbilt University, Nashville, TN, USA; Center of Structural Biology, Vanderbilt University, Nashville, TN, USA; Department of Biochemistry and Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN, USA.
  • Roy V; Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139, USA.
  • Fouch ME; Integral Molecular, Philadelphia, PA 19104, USA.
  • Kose N; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Trivette A; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Nargi RS; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Winkler ES; Department of Medicine, Washington University, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University, St. Louis, MO 63110, USA.
  • Kim AS; Department of Medicine, Washington University, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University, St. Louis, MO 63110, USA.
  • Gainza C; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Rodriguez J; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Armstrong E; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Sutton RE; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Reidy J; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Carnahan RH; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • McDonald WH; Department of Biochemistry and Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN, USA.
  • Schoeder CT; Center of Structural Biology, Vanderbilt University, Nashville, TN, USA; Department of Chemistry, Vanderbilt University, Nashville, TN, USA.
  • Klimstra WB; The Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 165261, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 165261, USA.
  • Davidson E; Integral Molecular, Philadelphia, PA 19104, USA.
  • Doranz BJ; Integral Molecular, Philadelphia, PA 19104, USA.
  • Alter G; Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139, USA.
  • Meiler J; Center of Structural Biology, Vanderbilt University, Nashville, TN, USA; Department of Chemistry, Vanderbilt University, Nashville, TN, USA; Institute for Drug Discovery, Leipzig University Medical School, Leipzig, Germany.
  • Schey KL; Department of Biochemistry and Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN, USA.
  • Julander JG; Institute for Antiviral Research, Utah State University, Logan, UT 84335, USA.
  • Diamond MS; Department of Medicine, Washington University, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University, St. Louis, MO 63110, USA.
  • Crowe JE; Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic a
Cell ; 184(17): 4430-4446.e22, 2021 08 19.
Article en En | MEDLINE | ID: mdl-34416147
ABSTRACT
Alphaviruses cause severe arthritogenic or encephalitic disease. The E1 structural glycoprotein is highly conserved in these viruses and mediates viral fusion with host cells. However, the role of antibody responses to the E1 protein in immunity is poorly understood. We isolated E1-specific human monoclonal antibodies (mAbs) with diverse patterns of recognition for alphaviruses (ranging from Eastern equine encephalitis virus [EEEV]-specific to alphavirus cross-reactive) from survivors of natural EEEV infection. Antibody binding patterns and epitope mapping experiments identified differences in E1 reactivity based on exposure of epitopes on the glycoprotein through pH-dependent mechanisms or presentation on the cell surface prior to virus egress. Therapeutic efficacy in vivo of these mAbs corresponded with potency of virus egress inhibition in vitro and did not require Fc-mediated effector functions for treatment against subcutaneous EEEV challenge. These studies reveal the molecular basis for broad and protective antibody responses to alphavirus E1 proteins.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteínas Virales / Alphavirus / Reacciones Cruzadas / Liberación del Virus / Anticuerpos Antivirales Límite: Animals / Female / Humans / Male Idioma: En Revista: Cell Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteínas Virales / Alphavirus / Reacciones Cruzadas / Liberación del Virus / Anticuerpos Antivirales Límite: Animals / Female / Humans / Male Idioma: En Revista: Cell Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos