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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Ruminant Diseases and Immunology Research » Research » Publications at this Location » Publication #416084
Research Project: Host-pathogen Interactions and Control Strategies for Bacterial Respiratory Pathogens in Cattle

Location: Ruminant Diseases and Immunology Research

Title: Altered germinal center responses in mice vaccinated with highly pathogenic avian influenza A(H5N1) virus

Author
item SEILER, PATRICK - St Jude Children’s Research Hospital
item Kaplan, Bryan
item BRICE, DAVID - St Jude Children’s Research Hospital
item DUAN, SUSU - St Jude Children’s Research Hospital
item LI, LEI - St Jude Children’s Research Hospital
item MCGARGILL, MAUREEN - St Jude Children’s Research Hospital
item LEE, NATALIE - St Jude Children’s Research Hospital
item LIN, CHUN-YANG - St Jude Children’s Research Hospital
item KEATING, RACHAEL - St Jude Children’s Research Hospital
item GOVORKOVA, ELENA - St Jude Children’s Research Hospital
item WEBBY, RICHARD - St Jude Children’s Research Hospital

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/21/2025
Publication Date: 5/27/2025
Citation: Seiler, P., Kaplan, B.S., Brice, D.C., Duan, S., Li, L., Mcgargill, M.A., Lee, N., Lin, C., Keating, R., Govorkova, E.A., Webby, R.J. 2025. Altered germinal center responses in mice vaccinated with highly pathogenic avian influenza A(H5N1) virus. Vaccine. 60. Article 127311. https://doi.org/10.1016/j.vaccine.2025.127311.
DOI: https://doi.org/10.1016/j.vaccine.2025.127311

Interpretive Summary: Vaccines are the most effective and widespread intervention against influenza A viruses (IAV). Development and stockpiling of vaccines to protect against future IAV pandemics is common practice for public health preparedness. In animal models, vaccines against highly pathogenic avian influenza (HPAI) H5N1 virus produce lower neutralizing antibody responses when compared to seasonal H1N1 IAV vaccines. To understand this phenomenon, the cellular responses in the draining lymph nodes of mice were compared following vaccination against H5N1, H1N1, and other IAV subtypes. In mice that received H5N1 vaccine, fewer germinal centers were observed in the draining lymph nodes. Additionally, fewer pro-inflammatory germinal center resident T cell, Tfh, that trigger antibody production from B cells were observed compared to mice that received H1N1 vaccine. These data suggest the differences in neutralizing antibody production in mice could be due to germinal center reaction formation and composition in the draining lymph nodes.

Technical Abstract: Highly pathogenic avian influenza (HPAI) H5N1 virus vaccines yield lower neutralizing antibody titers in animal models than do seasonal or emerging influenza A virus (IAV) vaccines. To understand these differences, we compared the cellular immune responses in the draining lymph nodes (dLNs) of mice vaccinated with HPAI H5N1 to those in mice vaccinated with seasonal H1N1pdm09 and emerging H7N9 or H9N2 IAV. H5N1-vaccinated mice exhibited reduced serum neutralizing antibody titers, despite the hemagglutinin-binding immunoglobulin production being similar to other IAV vaccines. Although bulk RNA sequencing showed no differences in B-cell populations after H5N1 and H1N1pdm09 vaccination, H5N1 vaccination resulted in fewer, but larger, dLN germinal centers and significantly more extrafollicular B cells, which produce lower neutralizing antibody titers. Furthermore, H5N1-vaccinated mice had significantly more follicular helper and regulatory T cells. Therefore, differences in neutralizing antibody production in mice after IAV vaccination could be due to sutype-dependent germinal center reactions in the dLNs.