Your browser doesn't support javascript.
loading
Development of a Human Antibody Cocktail that Deploys Multiple Functions to Confer Pan-Ebolavirus Protection.
Wec, Anna Z; Bornholdt, Zachary A; He, Shihua; Herbert, Andrew S; Goodwin, Eileen; Wirchnianski, Ariel S; Gunn, Bronwyn M; Zhang, Zirui; Zhu, Wenjun; Liu, Guodong; Abelson, Dafna M; Moyer, Crystal L; Jangra, Rohit K; James, Rebekah M; Bakken, Russell R; Bohorova, Natasha; Bohorov, Ognian; Kim, Do H; Pauly, Michael H; Velasco, Jesus; Bortz, Robert H; Whaley, Kevin J; Goldstein, Tracey; Anthony, Simon J; Alter, Galit; Walker, Laura M; Dye, John M; Zeitlin, Larry; Qiu, Xiangguo; Chandran, Kartik.
Afiliação
  • Wec AZ; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • Bornholdt ZA; Mapp Biopharmaceutical, San Diego, CA 92121, USA.
  • He S; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada.
  • Herbert AS; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
  • Goodwin E; Adimab, LLC, Lebanon, NH 03766, USA.
  • Wirchnianski AS; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • Gunn BM; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Zhang Z; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada.
  • Zhu W; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada.
  • Liu G; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada.
  • Abelson DM; Mapp Biopharmaceutical, San Diego, CA 92121, USA.
  • Moyer CL; Mapp Biopharmaceutical, San Diego, CA 92121, USA.
  • Jangra RK; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • James RM; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
  • Bakken RR; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
  • Bohorova N; Mapp Biopharmaceutical, San Diego, CA 92121, USA.
  • Bohorov O; Mapp Biopharmaceutical, San Diego, CA 92121, USA.
  • Kim DH; Mapp Biopharmaceutical, San Diego, CA 92121, USA.
  • Pauly MH; Mapp Biopharmaceutical, San Diego, CA 92121, USA.
  • Velasco J; Mapp Biopharmaceutical, San Diego, CA 92121, USA.
  • Bortz RH; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • Whaley KJ; Mapp Biopharmaceutical, San Diego, CA 92121, USA.
  • Goldstein T; One Health Institute and Karen C. Drayer Wildlife Health Center, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
  • Anthony SJ; Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
  • Alter G; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Walker LM; Adimab, LLC, Lebanon, NH 03766, USA.
  • Dye JM; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
  • Zeitlin L; Mapp Biopharmaceutical, San Diego, CA 92121, USA. Electronic address: larry.zeitlin@mappbio.com.
  • Qiu X; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada. Electronic address: xiangguo.qiu@canada.ca.
  • Chandran K; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: kartik.chandran@einstein.yu.edu.
Cell Host Microbe ; 25(1): 39-48.e5, 2019 01 09.
Article em En | MEDLINE | ID: mdl-30629917
ABSTRACT
Passive administration of monoclonal antibodies (mAbs) is a promising therapeutic approach for Ebola virus disease (EVD). However, all mAbs and mAb cocktails that have entered clinical development are specific for a single member of the Ebolavirus genus, Ebola virus (EBOV), and ineffective against outbreak-causing Bundibugyo virus (BDBV) and Sudan virus (SUDV). Here, we advance MBP134, a cocktail of two broadly neutralizing human mAbs, ADI-15878 from an EVD survivor and ADI-23774 from the same survivor but specificity-matured for SUDV GP binding affinity, as a candidate pan-ebolavirus therapeutic. MBP134 potently neutralized all ebolaviruses and demonstrated greater protective efficacy than ADI-15878 alone in EBOV-challenged guinea pigs. A second-generation cocktail, MBP134AF, engineered to effectively harness natural killer (NK) cells afforded additional improvement relative to its precursor in protective efficacy against EBOV and SUDV in guinea pigs. MBP134AF is an optimized mAb cocktail suitable for evaluation as a pan-ebolavirus therapeutic in nonhuman primates.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença pelo Vírus Ebola / Ebolavirus / Anticorpos Monoclonais / Anticorpos Antivirais Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2019 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: Doença pelo Vírus Ebola / Ebolavirus / Anticorpos Monoclonais / Anticorpos Antivirais Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article