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Design and characterization of protective pan-ebolavirus and pan-filovirus bispecific antibodies.
Wirchnianski, Ariel S; Nyakatura, Elisabeth K; Herbert, Andrew S; Kuehne, Ana I; Abbasi, Shawn A; Florez, Catalina; Storm, Nadia; McKay, Lindsay G A; Dailey, Leandrew; Kuang, Erin; Abelson, Dafna M; Wec, Anna Z; Chakraborti, Srinjoy; Holtsberg, Frederick W; Shulenin, Sergey; Bornholdt, Zachary A; Aman, M Javad; Honko, Anna N; Griffiths, Anthony; Dye, John M; Chandran, Kartik; Lai, Jonathan R.
Afiliação
  • Wirchnianski AS; Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, United States of America.
  • Nyakatura EK; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America.
  • Herbert AS; Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, United States of America.
  • Kuehne AI; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America.
  • Abbasi SA; The Geneva Foundation, Tacoma, Washington, United States of America.
  • Florez C; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America.
  • Storm N; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America.
  • McKay LGA; The Geneva Foundation, Tacoma, Washington, United States of America.
  • Dailey L; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America.
  • Kuang E; The Geneva Foundation, Tacoma, Washington, United States of America.
  • Abelson DM; Department of Virology, Immunology, and Microbiology; and National Emerging Infectious Diseases Laboratories, Boston University School of Medicine, Boston, Massachusetts, United States of America.
  • Wec AZ; Department of Virology, Immunology, and Microbiology; and National Emerging Infectious Diseases Laboratories, Boston University School of Medicine, Boston, Massachusetts, United States of America.
  • Chakraborti S; Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, United States of America.
  • Holtsberg FW; Mapp Biopharmaceutical Inc., San Diego, California, United States of America.
  • Shulenin S; Mapp Biopharmaceutical Inc., San Diego, California, United States of America.
  • Bornholdt ZA; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America.
  • Aman MJ; Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, United States of America.
  • Honko AN; Integrated BioTherapeutics, Inc., Rockville, Maryland, United States of America.
  • Griffiths A; Integrated BioTherapeutics, Inc., Rockville, Maryland, United States of America.
  • Dye JM; Mapp Biopharmaceutical Inc., San Diego, California, United States of America.
  • Chandran K; Integrated BioTherapeutics, Inc., Rockville, Maryland, United States of America.
  • Lai JR; Department of Virology, Immunology, and Microbiology; and National Emerging Infectious Diseases Laboratories, Boston University School of Medicine, Boston, Massachusetts, United States of America.
PLoS Pathog ; 20(4): e1012134, 2024 Apr.
Article em En | MEDLINE | ID: mdl-38603762
ABSTRACT
Monoclonal antibodies (mAbs) are an important class of antiviral therapeutics. MAbs are highly selective, well tolerated, and have long in vivo half-life as well as the capacity to induce immune-mediated virus clearance. Their activities can be further enhanced by integration of their variable fragments (Fvs) into bispecific antibodies (bsAbs), affording simultaneous targeting of multiple epitopes to improve potency and breadth and/or to mitigate against viral escape by a single mutation. Here, we explore a bsAb strategy for generation of pan-ebolavirus and pan-filovirus immunotherapeutics. Filoviruses, including Ebola virus (EBOV), Sudan virus (SUDV), and Marburg virus (MARV), cause severe hemorrhagic fever. Although there are two FDA-approved mAb therapies for EBOV infection, these do not extend to other filoviruses. Here, we combine Fvs from broad ebolavirus mAbs to generate novel pan-ebolavirus bsAbs that are potently neutralizing, confer protection in mice, and are resistant to viral escape. Moreover, we combine Fvs from pan-ebolavirus mAbs with those of protective MARV mAbs to generate pan-filovirus protective bsAbs. These results provide guidelines for broad antiviral bsAb design and generate new immunotherapeutic candidates.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Anticorpos Biespecíficos / Doença pelo Vírus Ebola / Ebolavirus / Anticorpos Antivirais Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Anticorpos Biespecíficos / Doença pelo Vírus Ebola / Ebolavirus / Anticorpos Antivirais Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article