skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus

Abstract

Research highlights: {yields} The fusion peptide is the only universally conserved epitope in all influenza viral hemagglutinins. {yields} Anti-fusion peptide antibodies are universal antibodies that cross-react with all influenza HA subtypes. {yields} The universal antibodies cross-neutralize different influenza A subtypes. {yields} The universal antibodies inhibit the fusion process between the viruses and the target cells. -- Abstract: The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it could be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by themore » antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses.« less

Authors:
 [1];  [2];  [3];  [4]; ;  [5]; ;  [1];  [6];  [4];  [6];  [1];  [3]
  1. Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada)
  2. (Saudi Arabia)
  3. (Canada)
  4. National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB (Canada)
  5. National Institute for the Control of Pharmaceutical and Biological Products, Beijing (China)
  6. Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States)
Publication Date:
OSTI Identifier:
22204709
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 403; Journal Issue: 2; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMINO ACIDS; CELL CULTURES; EGGS; HEMAGGLUTININS; INFLUENZA; INFLUENZA VIRUSES; PEPTIDES; PH VALUE; VACCINES

Citation Formats

Hashem, Anwar M., Department of Microbiology, Faculty of Medicine, King Abdulaziz University, Jeddah, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Van Domselaar, Gary, Li, Changgui, Wang, Junzhi, She, Yi-Min, Cyr, Terry D., Sui, Jianhua, He, Runtao, Marasco, Wayne A., Li, Xuguang, E-mail: Sean.Li@hc-sc.gc.ca, and Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON. Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus. United States: N. p., 2010. Web. doi:10.1016/J.BBRC.2010.11.030.
Hashem, Anwar M., Department of Microbiology, Faculty of Medicine, King Abdulaziz University, Jeddah, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Van Domselaar, Gary, Li, Changgui, Wang, Junzhi, She, Yi-Min, Cyr, Terry D., Sui, Jianhua, He, Runtao, Marasco, Wayne A., Li, Xuguang, E-mail: Sean.Li@hc-sc.gc.ca, & Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON. Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus. United States. doi:10.1016/J.BBRC.2010.11.030.
Hashem, Anwar M., Department of Microbiology, Faculty of Medicine, King Abdulaziz University, Jeddah, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Van Domselaar, Gary, Li, Changgui, Wang, Junzhi, She, Yi-Min, Cyr, Terry D., Sui, Jianhua, He, Runtao, Marasco, Wayne A., Li, Xuguang, E-mail: Sean.Li@hc-sc.gc.ca, and Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON. Fri . "Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus". United States. doi:10.1016/J.BBRC.2010.11.030.
@article{osti_22204709,
title = {Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus},
author = {Hashem, Anwar M. and Department of Microbiology, Faculty of Medicine, King Abdulaziz University, Jeddah and Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON and Van Domselaar, Gary and Li, Changgui and Wang, Junzhi and She, Yi-Min and Cyr, Terry D. and Sui, Jianhua and He, Runtao and Marasco, Wayne A. and Li, Xuguang, E-mail: Sean.Li@hc-sc.gc.ca and Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON},
abstractNote = {Research highlights: {yields} The fusion peptide is the only universally conserved epitope in all influenza viral hemagglutinins. {yields} Anti-fusion peptide antibodies are universal antibodies that cross-react with all influenza HA subtypes. {yields} The universal antibodies cross-neutralize different influenza A subtypes. {yields} The universal antibodies inhibit the fusion process between the viruses and the target cells. -- Abstract: The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it could be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by the antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses.},
doi = {10.1016/J.BBRC.2010.11.030},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 403,
place = {United States},
year = {2010},
month = {12}
}