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Anti-neuraminidase and anti-HA stalk antibodies reduce the susceptibility to and infectivity of influenza A/H3N2 virus

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Listed:
  • Gregory Hoy

    (University of Michigan, School of Public Health)

  • Thomas Cortier

    (Université Paris Cité INSERM U1332, Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur
    Sorbonne Université, Collège Doctoral)

  • Hannah E. Maier

    (University of Michigan, School of Public Health)

  • Guillermina Kuan

    (Sustainable Sciences Institute
    Centro de Salud Sócrates Flores Vivas, Ministry of Health)

  • Roger Lopez

    (Sustainable Sciences Institute
    Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Laboratorio Nacional de Virología)

  • Nery Sanchez

    (Sustainable Sciences Institute)

  • Sergio Ojeda

    (Sustainable Sciences Institute)

  • Miguel Plazaola

    (Sustainable Sciences Institute)

  • Daniel Stadlbauer

    (Icahn School of Medicine at Mount Sinai, Department of Microbiology, Icahn School of Medicine at Mount Sinai)

  • Abigail Shotwell

    (University of Michigan, School of Public Health)

  • Angel Balmaseda

    (Sustainable Sciences Institute
    Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Laboratorio Nacional de Virología)

  • Florian Krammer

    (Icahn School of Medicine at Mount Sinai, Department of Microbiology, Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai, Center for Vaccine Research and Pandemic Preparedness (C-VaRPP)
    Icahn School of Medicine at Mount Sinai, Department of Pathology, Molecular and Cell-Based Medicine
    Medical University of Vienna, Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research)

  • Simon Cauchemez

    (Université Paris Cité INSERM U1332, Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur)

  • Aubree Gordon

    (University of Michigan, School of Public Health)

Abstract

Immune responses against neuraminidase (NA) and hemagglutinin (HA) are critical for developing effective influenza vaccines, yet their role in influenza transmission remains unclear. We conducted household transmission studies in Managua, Nicaragua, to assess the impact of anti-NA and anti-HA antibodies induced by natural infection on influenza A/H3N2 susceptibility and infectivity. Using mathematical models capturing household transmission dynamics, we found that high pre-existing antibody levels against the HA head (>31, [95% CrI 13–67]), HA stalk (>35, [95% CrI 11–66]), and NA (>31, [95% CrI 12–68]) are associated with reduced susceptibility to infection (relative susceptibility: HA head, 0.63 [95% CrI 0.42–0.98]; HA stalk, 0.66 [95% CrI 0.44–0.99]; NA, 0.49 [95% CrI 0.30–0.76]). HA stalk (>58 [95% CrI: 47–70]) and NA (>27 [95% CrI: 15–43]) are associated with reduced infectivity (relative infectivity: NA, 0.55 [95% CrI: 0.32–0.98], HA stalk 0.53 [95% CrI: 0.27–0.97]). These findings suggest that influenza vaccines designed to elicit NA immunity in addition to HA immunity may not only enhance protection against infection but also reduce onward transmission.

Suggested Citation

  • Gregory Hoy & Thomas Cortier & Hannah E. Maier & Guillermina Kuan & Roger Lopez & Nery Sanchez & Sergio Ojeda & Miguel Plazaola & Daniel Stadlbauer & Abigail Shotwell & Angel Balmaseda & Florian Kramm, 2025. "Anti-neuraminidase and anti-HA stalk antibodies reduce the susceptibility to and infectivity of influenza A/H3N2 virus," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65283-0
    DOI: 10.1038/s41467-025-65283-0
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