Abstract

Tissue-resident memory (TRM) CD8+ T-cells play a crucial role in the protection against influenza infection but remain difficult to elicit using recombinant protein vaccines. OVX836 is a recombinant protein vaccine, obtained by the fusion of the DNA sequence of the influenza A nucleoprotein (NP) to the DNA sequence of the OVX313 heptamerization domain. We previously demonstrated that OVX836 provides broad-spectrum protection against influenza viruses. Here, we show that OVX836 intramuscular (IM) immunization induces higher numbers of NP-specific IFNγ-producing CD8+ T-cells in the lung, compared to mutant NP (NPm) and wild-type NP (NPwt), which form monomeric and trimeric structures, respectively. OVX836 induces cytotoxic CD8+ T-cells and high frequencies of lung TRM CD8+ T-cells, while inducing solid protection against lethal influenza virus challenges for at least 90 days. Adoptive transfer experiments demonstrated that protection against diverse influenza subtypes is mediated by NP-specific CD8+ T-cells isolated from the lung and spleen following OVX836 vaccination. OVX836 induces a high number of NP-specific lung CD8+ TRM-cells for long-term protection against influenza viruses.

Highlights

  • Influenza A infection is a major cause of respiratory infections worldwide

  • Our findings demonstrate that the OVX836 vaccine, when compared to NPm and NP wild type (NPwt), generates higher proportions of lung Tissue-resident memory (TRM) CD8+ T-cells with cytotoxic activity, producing a higher level of protection against influenza viruses

  • NPwt and OVX836 thermally unfolded at 75–76°C, a relatively high temperature, as compared to that of NPm (52–53°C)

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Summary

Introduction

Influenza A infection is a major cause of respiratory infections worldwide. Seasonal flu epidemics occur each year in autumn and winter, with a prevalence of 5 to 10%. They are caused by A/H1N1, A/H3N2, and B-type influenza viruses. Most seasonal influenza infections are benign, they can cause hospitalization in severe cases, and even death in at-risk populations. OVX836 Induces CD8+ TRM Responses die from influenza around the world (https://www.who.int/ influenza/surveillance_monitoring/en/). The “at-risk” populations include elderly people, children, immunosuppressed individuals, and people with chronic diseases

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