Your browser doesn't support javascript.
loading
Immunization-Elicited Broadly Protective Antibody Reveals Ebolavirus Fusion Loop as a Site of Vulnerability.
Zhao, Xuelian; Howell, Katie A; He, Shihua; Brannan, Jennifer M; Wec, Anna Z; Davidson, Edgar; Turner, Hannah L; Chiang, Chi-I; Lei, Lin; Fels, J Maximilian; Vu, Hong; Shulenin, Sergey; Turonis, Ashley N; Kuehne, Ana I; Liu, Guodong; Ta, Mi; Wang, Yimeng; Sundling, Christopher; Xiao, Yongli; Spence, Jennifer S; Doranz, Benjamin J; Holtsberg, Frederick W; Ward, Andrew B; Chandran, Kartik; Dye, John M; Qiu, Xiangguo; Li, Yuxing; Aman, M Javad.
Afiliación
  • Zhao X; Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20878, USA.
  • Howell KA; Integrated BioTherapeutics, Rockville, MD 20850, USA.
  • He S; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada; Deparment of Medical Microbiology, University of Manitoba, MB R3E 0J9, Canada.
  • Brannan JM; US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21701, USA.
  • Wec AZ; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • Davidson E; Integral Molecular, Philadelphia, PA 19104, USA.
  • Turner HL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Chiang CI; Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20878, USA.
  • Lei L; Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20878, USA.
  • Fels JM; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • Vu H; Integrated BioTherapeutics, Rockville, MD 20850, USA.
  • Shulenin S; Integrated BioTherapeutics, Rockville, MD 20850, USA.
  • Turonis AN; Integrated BioTherapeutics, Rockville, MD 20850, USA.
  • Kuehne AI; US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21701, USA.
  • Liu G; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada; Deparment of Medical Microbiology, University of Manitoba, MB R3E 0J9, Canada.
  • Ta M; Integral Molecular, Philadelphia, PA 19104, USA.
  • Wang Y; Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20878, USA.
  • Sundling C; Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
  • Xiao Y; Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Spence JS; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • Doranz BJ; Integral Molecular, Philadelphia, PA 19104, USA.
  • Holtsberg FW; Integrated BioTherapeutics, Rockville, MD 20850, USA.
  • Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Chandran K; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • Dye JM; US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21701, USA.
  • Qiu X; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada; Deparment of Medical Microbiology, University of Manitoba, MB R3E 0J9, Canada.
  • Li Y; Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20878, USA; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: liy@ibbr.umd.edu.
  • Aman MJ; Integrated BioTherapeutics, Rockville, MD 20850, USA. Electronic address: javad@integratedbiotherapeutics.com.
Cell ; 169(5): 891-904.e15, 2017 May 18.
Article en En | MEDLINE | ID: mdl-28525756
ABSTRACT
While neutralizing antibodies are highly effective against ebolavirus infections, current experimental ebolavirus vaccines primarily elicit species-specific antibody responses. Here, we describe an immunization-elicited macaque antibody (CA45) that clamps the internal fusion loop with the N terminus of the ebolavirus glycoproteins (GPs) and potently neutralizes Ebola, Sudan, Bundibugyo, and Reston viruses. CA45, alone or in combination with an antibody that blocks receptor binding, provided full protection against all pathogenic ebolaviruses in mice, guinea pigs, and ferrets. Analysis of memory B cells from the immunized macaque suggests that elicitation of broadly neutralizing antibodies (bNAbs) for ebolaviruses is possible but difficult, potentially due to the rarity of bNAb clones and their precursors. Unexpectedly, germline-reverted CA45, while exhibiting negligible binding to full-length GP, bound a proteolytically remodeled GP with picomolar affinity, suggesting that engineered ebolavirus vaccines could trigger rare bNAb precursors more robustly. These findings have important implications for developing pan-ebolavirus vaccine and immunotherapeutic cocktails.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Fiebre Hemorrágica Ebola / Vacunas contra el Virus del Ébola / Anticuerpos Neutralizantes / Anticuerpos Antivirales Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cell Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Fiebre Hemorrágica Ebola / Vacunas contra el Virus del Ébola / Anticuerpos Neutralizantes / Anticuerpos Antivirales Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cell Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos