tetano
Editor, Senior Moderator
Front Immunol
. 2021 Jun 10;12:678483.
doi: 10.3389/fimmu.2021.678483. eCollection 2021.
OVX836 Heptameric Nucleoprotein Vaccine Generates Lung Tissue-Resident Memory CD8+ T-Cells for Cross-Protection Against Influenza
Judith Del Campo[SUP] 1 [/SUP], Julien Bouley[SUP] 1 [/SUP], Marion Chevandier[SUP] 1 [/SUP], Carine Rousset[SUP] 1 [/SUP], Marjorie Haller[SUP] 1 [/SUP], Alice Indalecio[SUP] 1 [/SUP], Delphine Guyon-Gellin[SUP] 1 [/SUP], Alexandre Le Vert[SUP] 1 [/SUP], Fergal Hill[SUP] 1 [/SUP], Sophia Djebali[SUP] 2 [/SUP], Yann Leverrier[SUP] 2 [/SUP], Jacqueline Marvel[SUP] 2 [/SUP], Béhazine Combadière[SUP] 3 [/SUP], Florence Nicolas[SUP] 1 [/SUP]
Affiliations
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.
Keywords: CD8+ T-cells; cellular immunity; influenza vaccine; protection; recombinant nucleoprotein.
. 2021 Jun 10;12:678483.
doi: 10.3389/fimmu.2021.678483. eCollection 2021.
OVX836 Heptameric Nucleoprotein Vaccine Generates Lung Tissue-Resident Memory CD8+ T-Cells for Cross-Protection Against Influenza
Judith Del Campo[SUP] 1 [/SUP], Julien Bouley[SUP] 1 [/SUP], Marion Chevandier[SUP] 1 [/SUP], Carine Rousset[SUP] 1 [/SUP], Marjorie Haller[SUP] 1 [/SUP], Alice Indalecio[SUP] 1 [/SUP], Delphine Guyon-Gellin[SUP] 1 [/SUP], Alexandre Le Vert[SUP] 1 [/SUP], Fergal Hill[SUP] 1 [/SUP], Sophia Djebali[SUP] 2 [/SUP], Yann Leverrier[SUP] 2 [/SUP], Jacqueline Marvel[SUP] 2 [/SUP], Béhazine Combadière[SUP] 3 [/SUP], Florence Nicolas[SUP] 1 [/SUP]
Affiliations
- PMID: 34177921
- PMCID: PMC8223747
- DOI: 10.3389/fimmu.2021.678483
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.
Keywords: CD8+ T-cells; cellular immunity; influenza vaccine; protection; recombinant nucleoprotein.