Antigenic and structural analysis of the influenza hemagglutinin lateral patch
- 1Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- 2Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA
Abstract
The lateral patch epitope of the H1 hemagglutinin (HA) was a dominant target of antibodies following exposure to the 2009 pandemic H1N1 virus. However, the conservation and mechanisms of antigenic drift in the lateral patch remain unresolved. Here, we used lateral patch-specific monoclonal antibodies (mAbs) to understand the antigenicity of the lateral patch of human, avian, and swine H1Nx viruses spanning from 1918 to 2022. We found that lateral patch-specific mAbs demonstrated broad binding to pre-2009 H1N1 viruses and to the pandemic 2009 H1N1. However, we identified discrete mutations that drove multiple antibody evasion pathways for lateral patch-targeting mAbs in post-2009 H1N1 viruses. Despite this, we observed that the lateral patch remains well conserved across enzootic sources, suggesting that existing lateral patch antibodies could protect against a future zoonotic H1Nx pandemic. Together, these data support that the lateral patch remains an attractive target for pandemic preparedness against emergent H1Nx viruses.
IMPORTANCE: Seasonal influenza viruses continually undergo antigenic drift to evade antibody-mediated immunity, yet how individual antibody specificities shape this evolution remains poorly understood. We investigated the conservation and antigenic evolution of the H1 hemagglutinin (HA) lateral patch, an epitope targeted by broadly neutralizing antibodies. Using human monoclonal antibodies, we found that the lateral patch had remained highly conserved across nearly a century of human and animal influenza virus circulation but has undergone antigenic drift multiple times in pre- and post-2009 seasonal H1N1 viruses. Structural and mutational analyses revealed how these substitutions alter antibody recognition and shape the genetic features of lateral patch-targeting antibodies across individuals born in different eras. The lateral patch is also conserved among swine and avian H1Nx viruses, highlighting its potential as a target of protective immunity against pandemic H1Nx viruses. These findings provide a comprehensive framework for understanding antibody-driven evolution within a broadly conserved influenza virus epitope.
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BibTeX
@article{lemusreyes2026antigenic,
title = {{Antigenic and structural analysis of the influenza hemagglutinin lateral patch}},
author = {Jordan I. Lemus-Reyes and Monica L. Fernández-Quintero and Edgardo Ayala and Olivia M. Swanson and Marina R. Good and Wei Ji and Devika Suja and Julianna Han and Andrew B. Ward and Jenna J. Guthmiller},
journal = {Journal of Virology},
year = {2026},
month = sep,
doi = {10.1128/jvi.01265-26},
url = {https://doi.org/10.1128/jvi.01265-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Antigenic and structural analysis of the influenza hemagglutinin lateral patch
AU - Jordan I. Lemus-Reyes
AU - Monica L. Fernández-Quintero
AU - Edgardo Ayala
AU - Olivia M. Swanson
AU - Marina R. Good
AU - Wei Ji
AU - Devika Suja
AU - Julianna Han
AU - Andrew B. Ward
AU - Jenna J. Guthmiller
PY - 2026
DA - 2026/09/23
JO - Journal of Virology
DO - 10.1128/jvi.01265-26
UR - https://doi.org/10.1128/jvi.01265-26
AB - The lateral patch epitope of the H1 hemagglutinin (HA) was a dominant target of antibodies following exposure to the 2009 pandemic H1N1 virus. However, the conservation and mechanisms of antigenic drift in the lateral patch remain unresolved. Here, we used lateral patch-specific monoclonal antibodies (mAbs) to understand the antigenicity of the lateral patch of human, avian, and swine H1Nx viruses spanning from 1918 to 2022. We found that lateral patch-specific mAbs demonstrated broad binding to pre-2009 H1N1 viruses and to the pandemic 2009 H1N1. However, we identified discrete mutations that drove multiple antibody evasion pathways for lateral patch-targeting mAbs in post-2009 H1N1 viruses. Despite this, we observed that the lateral patch remains well conserved across enzootic sources, suggesting that existing lateral patch antibodies could protect against a future zoonotic H1Nx pandemic. Together, these data support that the lateral patch remains an attractive target for pandemic preparedness against emergent H1Nx viruses. IMPORTANCE: Seasonal influenza viruses continually undergo antigenic drift to evade antibody-mediated immunity, yet how individual antibody specificities shape this evolution remains poorly understood. We investigated the conservation and antigenic evolution of the H1 hemagglutinin (HA) lateral patch, an epitope targeted by broadly neutralizing antibodies. Using human monoclonal antibodies, we found that the lateral patch had remained highly conserved across nearly a century of human and animal influenza virus circulation but has undergone antigenic drift multiple times in pre- and post-2009 seasonal H1N1 viruses. Structural and mutational analyses revealed how these substitutions alter antibody recognition and shape the genetic features of lateral patch-targeting antibodies across individuals born in different eras. The lateral patch is also conserved among swine and avian H1Nx viruses, highlighting its potential as a target of protective immunity against pandemic H1Nx viruses. These findings provide a comprehensive framework for understanding antibody-driven evolution within a broadly conserved influenza virus epitope.
SN - 0022-538X
SN - 1098-5514
ER -