Heterosubtypic cross-protection induced by whole inactivated influenza virus vaccine in mice: influence of the route of vaccine administration

Authors

  • Natalija Budimir,

    1. Department of Medical Microbiology, Molecular Virology Section, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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  • Aalzen de Haan,

    1. Department of Medical Microbiology, Molecular Virology Section, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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  • Tjarko Meijerhof,

    1. Department of Medical Microbiology, Molecular Virology Section, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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  • Emma Gostick,

    1. Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK
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  • David A. Price,

    1. Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK
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  • Anke Huckriede,

    Corresponding author
    1. Department of Medical Microbiology, Molecular Virology Section, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
    • Correspondence: Anke Huckriede, Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.

      E-mail: a.l.w.huckriede@umcg.nl

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  • Jan Wilschut

    1. Department of Medical Microbiology, Molecular Virology Section, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Abstract

Background

Development of influenza vaccines capable of inducing broad protection against different virus subtypes is necessary given the ever-changing viral genetic landscape. Previously, we showed that vaccination with whole inactivated virus (WIV) induces heterosubtypic protection against lethal virus infection in mice. Whole inactivated virus-induced cross-protection was found to be mediated primarily by flu-specific CD8+ T cells.

Objectives

As it has been demonstrated that the route of vaccine administration strongly influences both the quantity and quality of vaccine-induced immunity, in this study, we determined which route of WIV administration induces optimal heterosubtypic cross-protection.

Methods

We compared the magnitude of the immune response and heterosubtypic protection against lethal A/PR/8/34 (H1N1) infection after subcutaneous (SC), intramuscular (IM), and intranasal (IN) vaccination with A/NIBRG-14 (H5N1) WIV.

Results

Subcutaneous and IM administration was superior to IN administration of influenza WIV in terms of flu-specific CD8+ T-cell induction and protection of mice against lethal heterosubtypic challenge. Surprisingly, despite the very low flu-specific CD8+ T-cell responses detected in IN-vaccinated mice, these animals were partially protected, most likely due to cross-reactive IgA antibodies.

Conclusion

The results of this study show that the magnitude of WIV-induced flu-specific CD8+ T-cell activity depends on the applied vaccination route. We conclude that parenteral administration of WIV vaccine, in particular IM injection, is superior to IN vaccine delivery for the induction of heterosubtypic cross-protection and generally appears to elicit stronger immune responses than mucosal vaccination with WIV.

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