OVX836 Heptameric Nucleoprotein Vaccine Generates Lung Tissue-Resident Memory CD8+ T-Cells for Cross-Protection Against Influenza

Campo, Judith del; Bouley, J.; Chevandier, Marion; Rousset, Carine; Haller, Marjorie; Indalecio, Alice; Guyon-Gellin, Delphine; Vert, Alexandre Le; Hill, Fergal; Djebali, Sophia; Leverrier, Yann; Marvel, Jacqueline; Combadière, Béhazine; Nicolas, Frédéric

doi:10.3389/fimmu.2021.678483

Cited by 16 publications

(15 citation statements)

References 48 publications

(87 reference statements)

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“…Animal studies have demonstrated the ability of OVX836 to elicit humoral and cellular immunity – including tissue-resident and long-lasting CD8+ T-cells in the lungs - as well as protection in mice and ferrets against influenza A and B challenges ( 16 , 18 ).…”

Section: Introductionmentioning

confidence: 99%

Randomized, Double-Blind, Reference-Controlled, Phase 2a Study Evaluating the Immunogenicity and Safety of OVX836, A Nucleoprotein-Based Influenza Vaccine

et al. 2022

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OVX836 is a recombinant protein-based vaccine targeting the highly conserved influenza nucleoprotein (NP), which aims to confer a broad-spectrum protection against influenza. In a Phase 1 study, OVX836, administered intramuscularly, has been found safe and immunogenic. The 90µg and 180µg dose levels were selected to be further evaluated in this randomized, monocenter, reference-controlled (Influvac Tetra™: quadrivalent seasonal influenza subunit vaccine), parallel group, double-blind, Phase 2a study in 300 healthy volunteers, aged 18-65 years, during the 2019/2020 flu season. Safety, influenza-like illness episodes (ILI; based on the Flu-PRO® questionnaire) and immunogenicity were assessed up to 180 days post-vaccination. OVX836 was safe and presented a reactogenicity profile similar to Influvac Tetra. It induced a significant increase in terms of NP-specific interferon-gamma (IFNγ) spot forming cells (SFCs), NP-specific CD4+ T-cells (essentially polyfunctional cells) and anti-NP IgG responses. OVX836 was superior to Influvac Tetra for all immunological parameters related to NP, and the 180µg dose was significantly superior to the 90µg dose for SFCs and CD4+ T-cells expressing IFNγ. Both the CD4+ T-cell and the anti-NP IgG responses persisted up to Day 180. An efficacy signal was observed with OVX836 at 180µg through reduction of ILI episodes occurring during the flu season as of 14 days post-vaccination. In conclusion, these results encourage further clinical evaluation of OVX836 in order to confirm the signal of efficacy on ILIs and/or laboratory-confirmed influenza cases. NCT04192500 (https://clinicaltrials.gov/ct2/show/study/NCT04192500)

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Section: Introductionmentioning

confidence: 99%

Randomized, Double-Blind, Reference-Controlled, Phase 2a Study Evaluating the Immunogenicity and Safety of OVX836, A Nucleoprotein-Based Influenza Vaccine

et al. 2022

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“…has been shown to induce improved IgG, CD4 + and CD8 + T-cell responses, uptake of NP antigens into dendritic cells, broad protection against H1N1 and H3N2 lethal challenges in mice and can be used with inactivated influenza vaccines to increase protection ( 244 ). OVX836 vaccination also showed strong long-lasting cross-protection against lethal influenza challenges for a minimum of 90 days in mice ( 245 ). Recently, a phase I clinical trial of OVX836 in adults showed no adverse events across administrations or dosage levels.…”

Section: Recombinant Influenza Vaccinesmentioning

confidence: 99%

Recent Progress in Recombinant Influenza Vaccine Development Toward Heterosubtypic Immune Response

2022

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Flu, a viral infection caused by the influenza virus, is still a global public health concern with potential to cause seasonal epidemics and pandemics. Vaccination is considered the most effective protective strategy against the infection. However, given the high plasticity of the virus and the suboptimal immunogenicity of existing influenza vaccines, scientists are moving toward the development of universal vaccines. An important property of universal vaccines is their ability to induce heterosubtypic immunity, i.e., a wide immune response coverage toward different influenza subtypes. With the increasing number of studies and mounting evidence on the safety and efficacy of recombinant influenza vaccines (RIVs), they have been proposed as promising platforms for the development of universal vaccines. This review highlights the current progress and advances in the development of RIVs in the context of heterosubtypic immunity induction toward universal vaccine production. In particular, this review discussed existing knowledge on influenza and vaccine development, current hemagglutinin-based RIVs in the market and in the pipeline, other potential vaccine targets for RIVs (neuraminidase, matrix 1 and 2, nucleoprotein, polymerase acidic, and basic 1 and 2 antigens), and deantigenization process. This review also provided discussion points and future perspectives in looking at RIVs as potential universal vaccine candidates for influenza.

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“… 24 Antigen-specific memory CD8 + T cell immune response can be formed in healthy people that had been infected with influenza. 25 Influenza-specific CD8 + T cells play a key role in broadly cross-reactive immunity to influenza viruses because they recognize peptide fragments of 8–11 amino acids in length that are derived from highly conserved internal viral proteins in the context of MHC class I molecules. 26 Following activation, CD8 + T cells also secrete antiviral cytokines such as IL-2, IFN-γ, and TNF-α, which further recruit innate and adaptive immune cells to the sites of viral dissemination and induce antiviral responses in infected cells.…”

Section: Discussionmentioning

confidence: 99%

Anti-Interferon-γ Autoantibodies Impair T-Lymphocyte Responses in Patients with Talaromyces marneffei Infections

Chen¹,

Yang²,

Li³

et al. 2022

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Background: Although anti-IFN-γ autoantibodies predispose patients to Talaromyces marneffei infection, whether this is mediated by T cell attenuation remains elusive. Methods: Total peripheral blood mononuclear cells (PBMCs) from healthy donors or patients with T. marneffei infection were stimulated with M1 58−66 , and immunodominant influenza H1N1 peptide, or heat-inactivated T. marneffei in the presence of serum from anti-IFN-γ autoantibody-positive patients or healthy controls. The percentages of IFN-γ + TNF + CD8 + T cells and IFN-γ + CD4 + T cells were determined by flow cytometry and cytokines released in the supernatant were detected by Cytometric Bead Array. Furthermore, PBMCs from patients with T. marneffei infection and healthy individuals were stimulated with IFN-γ and anti-CD3/CD28 beads, and the levels of STAT1 and STAT3 phosphorylation were detected by Western blot. Results: The M1-reactive CD8 + T cells that expressed IFN-γ + TNF-α + of healthy controls were clearly reduced in serum with hightiter anti-IFN-γ autoantibodies. In addition, the CD4 + T cell response, designated by the expression of IFN-γ, against T. marneffei in PBMCs of patients were significantly decreased when cultured in high-titer anti-IFN-γ autoantibody serum culture, compared to the healthy compartments. Moreover, the release of the cytokines IFN-γ, TNF-α and IL-2 was significantly decreased, while IL-10 was significantly increased. There was no significant difference in the phosphorylation levels of STAT1 and STAT3 protein between patients and healthy controls after IFN-γ or anti-CD3/CD28 beads stimulation. Conclusion: Anti-IFN-γ autoantibodies presence in the serum inhibited CD4 + Th1 and CD8 + T cell immune responses. There was no congenital dysfunction of STAT1 and STAT3 in anti-IFN-γ autoantibody-positive patients with T. marneffei infection. These results suggest that the production of anti-IFN-γ autoAbs impair T-lymphocyte responses.

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OVX836 Heptameric Nucleoprotein Vaccine Generates Lung Tissue-Resident Memory CD8+ T-Cells for Cross-Protection Against Influenza

Cited by 16 publications

References 48 publications

Randomized, Double-Blind, Reference-Controlled, Phase 2a Study Evaluating the Immunogenicity and Safety of OVX836, A Nucleoprotein-Based Influenza Vaccine

Randomized, Double-Blind, Reference-Controlled, Phase 2a Study Evaluating the Immunogenicity and Safety of OVX836, A Nucleoprotein-Based Influenza Vaccine

Recent Progress in Recombinant Influenza Vaccine Development Toward Heterosubtypic Immune Response

Anti-Interferon-γ Autoantibodies Impair T-Lymphocyte Responses in Patients with Talaromyces marneffei Infections

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