Your browser doesn't support javascript.
loading
Isolation and Characterization of Broad and Ultrapotent Human Monoclonal Antibodies with Therapeutic Activity against Chikungunya Virus.
Smith, Scott A; Silva, Laurie A; Fox, Julie M; Flyak, Andrew I; Kose, Nurgun; Sapparapu, Gopal; Khomandiak, Solomiia; Khomadiak, Solomiia; Ashbrook, Alison W; Kahle, Kristen M; Fong, Rachel H; Swayne, Sherri; Doranz, Benjamin J; McGee, Charles E; Heise, Mark T; Pal, Pankaj; Brien, James D; Austin, S Kyle; Diamond, Michael S; Dermody, Terence S; Crowe, James E.
Afiliação
  • Smith SA; Department of Medicine, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
  • Silva LA; Department of Pediatrics, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
  • Fox JM; Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Flyak AI; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
  • Kose N; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
  • Sapparapu G; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
  • Khomadiak S; Department of Pediatrics, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
  • Ashbrook AW; Department of Pediatrics, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Elizabeth B. Lamb Center for Pediatric Resear
  • Kahle KM; Integral Molecular, Philadelphia, PA 19104, USA.
  • Fong RH; Integral Molecular, Philadelphia, PA 19104, USA.
  • Swayne S; Integral Molecular, Philadelphia, PA 19104, USA.
  • Doranz BJ; Integral Molecular, Philadelphia, PA 19104, USA.
  • McGee CE; Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
  • Heise MT; Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
  • Pal P; Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Brien JD; Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Austin SK; Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Diamond MS; Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Dermody TS; Department of Pediatrics, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Elizabeth B. Lamb Center for Pediatric Resear
  • Crowe JE; Department of Pediatrics, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Vaccine Center, Vanderbilt Univers
Cell Host Microbe ; 18(1): 86-95, 2015 Jul 08.
Article em En | MEDLINE | ID: mdl-26159721
ABSTRACT
Chikungunya virus (CHIKV) is a mosquito-transmitted RNA virus that causes acute febrile infection associated with polyarthralgia in humans. Mechanisms of protective immunity against CHIKV are poorly understood, and no effective therapeutics or vaccines are available. We isolated and characterized human monoclonal antibodies (mAbs) that neutralize CHIKV infectivity. Among the 30 mAbs isolated, 13 had broad and ultrapotent neutralizing activity (IC50 < 10 ng/ml), and all of these mapped to domain A of the E2 envelope protein. Potent inhibitory mAbs blocked post-attachment steps required for CHIKV membrane fusion, and several were protective in a lethal challenge model in immunocompromised mice, even when administered at late time points after infection. These highly protective mAbs could be considered for prevention or treatment of CHIKV infection, and their epitope location in domain A of E2 could be targeted for rational structure-based vaccine development.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Vírus Chikungunya / Imunização Passiva / Febre de Chikungunya / Anticorpos Monoclonais / Anticorpos Antivirais Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Vírus Chikungunya / Imunização Passiva / Febre de Chikungunya / Anticorpos Monoclonais / Anticorpos Antivirais Idioma: En Ano de publicação: 2015 Tipo de documento: Article