학술논문
A fully human monoclonal antibody possesses antibody-dependent cellular cytotoxicity (ADCC) activity against the H1 subtype of influenza A virus by targeting a conserved epitope at the HA1 protomer interface.
Document Type
Academic Journal
Author
Gao R; Department of Biology and Microbiology, South Dakota State University, Brookings, South Dakota, USA.; Wang Z; Department of Biology and Microbiology, South Dakota State University, Brookings, South Dakota, USA.; Uprety T; Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky, USA.; Sreenivasan CC; Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky, USA.; Sheng Z; Zuckerman Mind Brian Behavior Institute, Columbia University, New York, New York, USA.; Hause BM; Research and Development Division, Cambridge Technologies Inc, Worthington, Minnesota, USA.; Brunick C; Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota, USA.; Wu H; SAB Biotherapeutics, Sioux Falls, South Dakota, USA.; Luke T; SAB Biotherapeutics, Sioux Falls, South Dakota, USA.; Bausch CL; SAB Biotherapeutics, Sioux Falls, South Dakota, USA.; Sullivan EJ; SAB Biotherapeutics, Sioux Falls, South Dakota, USA.; Hoppe AD; Department of Chemistry and Biochemistry, South Dakota State University, Brookings, South Dakota, USA.; Huber VC; Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota, USA.; Wang D; Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky, USA.; Li F; Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky, USA.
Source
Publisher: Wiley-Liss Country of Publication: United States NLM ID: 7705876 Publication Model: Print Cited Medium: Internet ISSN: 1096-9071 (Electronic) Linking ISSN: 01466615 NLM ISO Abbreviation: J Med Virol Subsets: MEDLINE
Subject
Language
English
Abstract
The Diversitab TM system produces target specific high titer fully human polyclonal IgG immunoglobulins from transchromosomic (Tc) bovines shown to be safe and effective against multiple virulent pathogens in animal studies and Phase 1, 2 and 3 human clinical trials. We describe the functional properties of a human monoclonal antibody (mAb), 38C2, identified from this platform, which recognizes recombinant H1 hemagglutinins (HAs) and induces appreciable antibody-dependent cellular cytotoxicity (ADCC) activity in vitro. Interestingly, 38C2 monoclonal antibody demonstrated no detectable neutralizing activity against H1N1 virus in both hemagglutination inhibition and virus neutralization assays. Nevertheless, this human monoclonal antibody induced appreciable ADCC against cells infected with multiple H1N1 strains. The HA-binding activity of 38C2 was also demonstrated in flow cytometry using Madin-Darby canine kidney cells infected with multiple influenza A H1N1 viruses. Through further investigation with the enzyme-linked immunosorbent assay involving the HA peptide array and 3-dimensional structural modeling, we demonstrated that 38C2 appears to target a conserved epitope located at the HA1 protomer interface of H1N1 influenza viruses. A novel mode of HA-binding and in vitro ADCC activity pave the way for further evaluation of 38C2 as a potential therapeutic agent to treat influenza virus infections in humans.
(© 2023 Wiley Periodicals LLC.)
(© 2023 Wiley Periodicals LLC.)