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Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections.
Gilchuk, Iuliia; Gilchuk, Pavlo; Sapparapu, Gopal; Lampley, Rebecca; Singh, Vidisha; Kose, Nurgun; Blum, David L; Hughes, Laura J; Satheshkumar, Panayampalli S; Townsend, Michael B; Kondas, Ashley V; Reed, Zachary; Weiner, Zachary; Olson, Victoria A; Hammarlund, Erika; Raue, Hans-Peter; Slifka, Mark K; Slaughter, James C; Graham, Barney S; Edwards, Kathryn M; Eisenberg, Roselyn J; Cohen, Gary H; Joyce, Sebastian; Crowe, James E.
Afiliação
  • Gilchuk I; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Gilchuk P; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Veterans Administration Tennessee Valley Healthcare System, Nashville, TN 37332, USA.
  • Sapparapu G; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Lampley R; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Singh V; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Kose N; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Blum DL; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Hughes LJ; Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
  • Satheshkumar PS; Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
  • Townsend MB; Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
  • Kondas AV; Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
  • Reed Z; Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA; Laboratory Leadership Service, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
  • Weiner Z; Laboratory Leadership Service, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
  • Olson VA; Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
  • Hammarlund E; Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR 97006, USA.
  • Raue HP; Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR 97006, USA.
  • Slifka MK; Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR 97006, USA.
  • Slaughter JC; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Graham BS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
  • Edwards KM; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Eisenberg RJ; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Cohen GH; Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Joyce S; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Veterans Administration Tennessee Valley Healthcare System, Nashville, TN 37332, USA.
  • Crowe JE; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, US
Cell ; 167(3): 684-694.e9, 2016 Oct 20.
Article em En | MEDLINE | ID: mdl-27768891
ABSTRACT
Monkeypox (MPXV) and cowpox (CPXV) are emerging agents that cause severe human infections on an intermittent basis, and variola virus (VARV) has potential for use as an agent of bioterror. Vaccinia immune globulin (VIG) has been used therapeutically to treat severe orthopoxvirus infections but is in short supply. We generated a large panel of orthopoxvirus-specific human monoclonal antibodies (Abs) from immune subjects to investigate the molecular basis of broadly neutralizing antibody responses for diverse orthopoxviruses. Detailed analysis revealed the principal neutralizing antibody specificities that are cross-reactive for VACV, CPXV, MPXV, and VARV and that are determinants of protection in murine challenge models. Optimal protection following respiratory or systemic infection required a mixture of Abs that targeted several membrane proteins, including proteins on enveloped and mature virion forms of virus. This work reveals orthopoxvirus targets for human Abs that mediate cross-protective immunity and identifies new candidate Ab therapeutic mixtures to replace VIG.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções por Poxviridae / Anticorpos Neutralizantes / Anticorpos Monoclonais / Anticorpos Antivirais / Especificidade de Anticorpos Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções por Poxviridae / Anticorpos Neutralizantes / Anticorpos Monoclonais / Anticorpos Antivirais / Especificidade de Anticorpos Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article