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A Fc engineering approach to define functional humoral correlates of immunity against Ebola virus.
Gunn, Bronwyn M; Lu, Richard; Slein, Matthew D; Ilinykh, Philipp A; Huang, Kai; Atyeo, Caroline; Schendel, Sharon L; Kim, Jiyoung; Cain, Caitlin; Roy, Vicky; Suscovich, Todd J; Takada, Ayato; Halfmann, Peter J; Kawaoka, Yoshihiro; Pauthner, Matthias G; Momoh, Mambu; Goba, Augustine; Kanneh, Lansana; Andersen, Kristian G; Schieffelin, John S; Grant, Donald; Garry, Robert F; Saphire, Erica Ollmann; Bukreyev, Alexander; Alter, Galit.
Afiliação
  • Gunn BM; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Lu R; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Slein MD; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Ilinykh PA; Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX, USA; Galveston National Laboratory, Galveston, TX, USA.
  • Huang K; Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX, USA; Galveston National Laboratory, Galveston, TX, USA.
  • Atyeo C; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Schendel SL; La Jolla Institute for Immunology, La Jolla, CA, USA.
  • Kim J; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Cain C; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Roy V; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Suscovich TJ; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Takada A; Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
  • Halfmann PJ; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin - Madison, Madison, WI, USA.
  • Kawaoka Y; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin - Madison, Madison, WI, USA.
  • Pauthner MG; Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA, USA.
  • Momoh M; Viral Hemorrhagic Fever Program, Kenema Government Hospital, Kenema, Sierra Leone.
  • Goba A; Viral Hemorrhagic Fever Program, Kenema Government Hospital, Kenema, Sierra Leone.
  • Kanneh L; Viral Hemorrhagic Fever Program, Kenema Government Hospital, Kenema, Sierra Leone.
  • Andersen KG; Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA, USA; Scripps Research Translational Institute, La Jolla, CA, USA.
  • Schieffelin JS; Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA, USA.
  • Grant D; Viral Hemorrhagic Fever Program, Kenema Government Hospital, Kenema, Sierra Leone; Ministry of Health and Sanitation, Freetown, Sierra Leone.
  • Garry RF; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA.
  • Saphire EO; La Jolla Institute for Immunology, La Jolla, CA, USA. Electronic address: erica@lji.org.
  • Bukreyev A; Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX, USA; Galveston National Laboratory, Galveston, TX, USA; Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX, USA. Electronic address: abukreye@utmb.edu.
  • Alter G; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA. Electronic address: galter@partners.org.
Immunity ; 54(4): 815-828.e5, 2021 04 13.
Article em En | MEDLINE | ID: mdl-33852832
ABSTRACT
Protective Ebola virus (EBOV) antibodies have neutralizing activity and induction of antibody constant domain (Fc)-mediated innate immune effector functions. Efforts to enhance Fc effector functionality often focus on maximizing antibody-dependent cellular cytotoxicity, yet distinct combinations of functions could be critical for antibody-mediated protection. As neutralizing antibodies have been cloned from EBOV disease survivors, we sought to identify survivor Fc effector profiles to help guide Fc optimization strategies. Survivors developed a range of functional antibody responses, and we therefore applied a rapid, high-throughput Fc engineering platform to define the most protective profiles. We generated a library of Fc variants with identical antigen-binding fragments (Fabs) from an EBOV neutralizing antibody. Fc variants with antibody-mediated complement deposition and moderate natural killer (NK) cell activity demonstrated complete protective activity in a stringent in vivo mouse model. Our findings highlight the importance of specific effector functions in antibody-mediated protection, and the experimental platform presents a generalizable resource for identifying correlates of immunity to guide therapeutic antibody design.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fragmentos Fab das Imunoglobulinas / Fragmentos Fc das Imunoglobulinas / Doença pelo Vírus Ebola / Ebolavirus Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: Immunity Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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XML
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Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fragmentos Fab das Imunoglobulinas / Fragmentos Fc das Imunoglobulinas / Doença pelo Vírus Ebola / Ebolavirus Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: Immunity Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos