Generation of a protective murine monoclonal antibody against the stem of influenza hemagglutinins from group 1 viruses and identification of resistance mutations against it

English version

Autoři: Wei Wang ^aff001; Russell Vassell ^aff001; Hyo Sook Song ^aff001; Qiong Chen ^aff001; Paul W. Keller ^aff001; Swati Verma ^aff001; Esmeralda Alvarado-Facundo ^aff001; Hongquan Wan ^aff001; Falko Schmeisser ^aff001; Clement A. Meseda ^aff001; Jerry P. Weir ^aff001; Carol D. Weiss ^aff001
Působiště autorů: Division of Viral Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, United States of America ^aff001
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0222436

Souhrn

Vaccines that elicit broadly cross-neutralizing antibodies, including antibodies that target the conserved stem of hemagglutinin (HA), are being developed as a strategy for next-generation influenza vaccines that protect against influenza across multiple years. However, efficient induction of cross-neutralizing antibodies remains a challenge, and potential escape mutations have not been well characterized. Here we elicited cross-neutralizing antibodies by immunizing animals with the hemagglutinins from H5 and H9 subtype influenza A viruses that are sensitive to neutralization by stem antibodies. We further isolated and characterized an HA stem monoclonal antibody 4C2 that broadly neutralizes group 1 influenza viruses and identified HA mutations that reduced sensitivity to stem antibodies. Our results offer insights for next-generation influenza vaccine strategies for inducing cross-neutralizing antibodies.

Klíčová slova:

Biology and life sciences – Physiology – Antibody isotypes – Antibodies – Vaccination and immunization – Immunologic adjuvants – Biochemistry – Proteins – Immune system proteins – Organisms – Viruses – RNA viruses – Orthomyxoviruses – Influenza viruses – Microbiology – Medical microbiology – Microbial pathogens – Viral pathogens – Microbial mutation – Medicine and health sciences – Immune physiology – Immunology – Infectious diseases – Viral diseases – Influenza – Pathology and laboratory medicine – Pathogens – Public and occupational health – Preventive medicine – Research and analysis methods – Precipitation techniques – Immunoprecipitation – Immunologic techniques – Immunoassays – Enzyme-linked immunoassays

Zdroje

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Generation of a protective murine monoclonal antibody against the stem of influenza hemagglutinins from group 1 viruses and identification of resistance mutations against it

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