A protective and broadly binding antibody class engages the influenza virus hemagglutinin head at its stem interface.

Autor: Simmons HC; Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Finney J; Department of Integrative Immunobiology, Duke University, Durham, North Carolina, USA., Kotaki R; Department of Immunology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan., Adachi Y; Department of Immunology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan., Park Moseman A; Department of Integrative Immunobiology, Duke University, Durham, North Carolina, USA., Watanabe A; Department of Integrative Immunobiology, Duke University, Durham, North Carolina, USA., Song S; Department of Surgery, Duke University, Durham, North Carolina 27710, USA., Robinson-McCarthy LR; Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Le Sage V; Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Kuraoka M; Department of Integrative Immunobiology, Duke University, Durham, North Carolina, USA., Moseman EA; Department of Integrative Immunobiology, Duke University, Durham, North Carolina, USA., Kelsoe G; Department of Integrative Immunobiology, Duke University, Durham, North Carolina, USA., Takahashi Y; Department of Immunology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan., McCarthy KR; Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Jul 01. Date of Electronic Publication: 2024 Jul 01.
DOI: 10.1101/2023.12.13.571543
Abstrakt: Influenza infection and vaccination impart strain-specific immunity that protects against neither seasonal antigenic variants nor the next pandemic. However, antibodies directed to conserved sites can confer broad protection. Here we identify and characterize a class of human antibodies that engage a previously undescribed, conserved epitope on the influenza hemagglutinin (HA) protein. Prototype antibody S8V1-157 binds at the normally occluded interface between the HA head and stem. Antibodies to this HA head-stem interface epitope are non-neutralizing in vitro but protect against lethal influenza infection in mice. Antibody isotypes that direct clearance of infected cells enhance this protection. Head-stem interface antibodies bind to most influenza A serotypes and seasonal human variants, and are present at low frequencies in the memory B cell populations of multiple human donors. Vaccines designed to elicit these antibodies might contribute to "universal" influenza immunity.
Databáze: MEDLINE