Immunogenicity and Protective Potential of Mucosal Vaccine Formulations Based on Conserved Epitopes of Influenza A Viruses Fused to an Innovative Ring Nanoplatform in Mice and Chickens
Current inactivated vaccines against influenza A viruses (IAV) mainly induce immune responses against highly variable epitopes across strains and are mostly delivered parenterally, limiting the development of an effective mucosal immunity. In this study, we evaluated the potential of intranasal form...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:ce5eeb8fd4fc4f3c89ecec190951fa7b2021-11-11T12:14:23ZImmunogenicity and Protective Potential of Mucosal Vaccine Formulations Based on Conserved Epitopes of Influenza A Viruses Fused to an Innovative Ring Nanoplatform in Mice and Chickens1664-322410.3389/fimmu.2021.772550https://doaj.org/article/ce5eeb8fd4fc4f3c89ecec190951fa7b2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.772550/fullhttps://doaj.org/toc/1664-3224Current inactivated vaccines against influenza A viruses (IAV) mainly induce immune responses against highly variable epitopes across strains and are mostly delivered parenterally, limiting the development of an effective mucosal immunity. In this study, we evaluated the potential of intranasal formulations incorporating conserved IAV epitopes, namely the long alpha helix (LAH) of the stalk domain of hemagglutinin and three tandem repeats of the ectodomain of the matrix protein 2 (3M2e), as universal mucosal anti-IAV vaccines in mice and chickens. The IAV epitopes were grafted to nanorings, a novel platform technology for mucosal vaccination formed by the nucleoprotein (N) of the respiratory syncytial virus, in fusion or not with the C-terminal end of the P97 protein (P97c), a recently identified Toll-like receptor 5 agonist. Fusion of LAH to nanorings boosted the generation of LAH-specific systemic and local antibody responses as well as cellular immunity in mice, whereas the carrier effect of nanorings was less pronounced towards 3M2e. Mice vaccinated with chimeric nanorings bearing IAV epitopes in fusion with P97c presented modest LAH- or M2e-specific IgG titers in serum and were unable to generate a mucosal humoral response. In contrast, N-3M2e or N-LAH nanorings admixed with Montanide™ gel (MG) triggered strong specific humoral responses, composed of serum type 1/type 2 IgG and mucosal IgG and IgA, as well as cellular responses dominated by type 1/type 17 cytokine profiles. All mice vaccinated with the [N-3M2e + N-LAH + MG] formulation survived an H1N1 challenge and the combination of both N-3M2e and N-LAH nanorings with MG enhanced the clinical and/or virological protective potential of the preparation in comparison to individual nanorings. Chickens vaccinated parenterally or mucosally with N-LAH and N-3M2e nanorings admixed with Montanide™ adjuvants developed a specific systemic humoral response, which nonetheless failed to confer protection against heterosubtypic challenge with a highly pathogenic H5N8 strain. Thus, while the combination of N-LAH and N-3M2e nanorings with Montanide™ adjuvants shows promise as a universal mucosal anti-IAV vaccine in the mouse model, further experiments have to be conducted to extend its efficacy to poultry.Cynthia CalzasMolida MaoMathilde TurpaudQuentin ViboudJoelle MettierThomas FigueroaPierre BessièreAntoine ManginAntoine ManginLaura SedanoPierre-Louis HervéPierre-Louis HervéRomain VolmerMariette F. DucatezSteve BourgaultDenis ArchambaultRonan Le GofficChristophe ChevalierFrontiers Media S.A.articleinfluenza A viruseshighly pathogenic avian influenza virusmucosal vaccinesadjuvantsnanoparticlesM2e/HA2 subunit vaccinesImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
influenza A viruses highly pathogenic avian influenza virus mucosal vaccines adjuvants nanoparticles M2e/HA2 subunit vaccines Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
influenza A viruses highly pathogenic avian influenza virus mucosal vaccines adjuvants nanoparticles M2e/HA2 subunit vaccines Immunologic diseases. Allergy RC581-607 Cynthia Calzas Molida Mao Mathilde Turpaud Quentin Viboud Joelle Mettier Thomas Figueroa Pierre Bessière Antoine Mangin Antoine Mangin Laura Sedano Pierre-Louis Hervé Pierre-Louis Hervé Romain Volmer Mariette F. Ducatez Steve Bourgault Denis Archambault Ronan Le Goffic Christophe Chevalier Immunogenicity and Protective Potential of Mucosal Vaccine Formulations Based on Conserved Epitopes of Influenza A Viruses Fused to an Innovative Ring Nanoplatform in Mice and Chickens |
| description |
Current inactivated vaccines against influenza A viruses (IAV) mainly induce immune responses against highly variable epitopes across strains and are mostly delivered parenterally, limiting the development of an effective mucosal immunity. In this study, we evaluated the potential of intranasal formulations incorporating conserved IAV epitopes, namely the long alpha helix (LAH) of the stalk domain of hemagglutinin and three tandem repeats of the ectodomain of the matrix protein 2 (3M2e), as universal mucosal anti-IAV vaccines in mice and chickens. The IAV epitopes were grafted to nanorings, a novel platform technology for mucosal vaccination formed by the nucleoprotein (N) of the respiratory syncytial virus, in fusion or not with the C-terminal end of the P97 protein (P97c), a recently identified Toll-like receptor 5 agonist. Fusion of LAH to nanorings boosted the generation of LAH-specific systemic and local antibody responses as well as cellular immunity in mice, whereas the carrier effect of nanorings was less pronounced towards 3M2e. Mice vaccinated with chimeric nanorings bearing IAV epitopes in fusion with P97c presented modest LAH- or M2e-specific IgG titers in serum and were unable to generate a mucosal humoral response. In contrast, N-3M2e or N-LAH nanorings admixed with Montanide™ gel (MG) triggered strong specific humoral responses, composed of serum type 1/type 2 IgG and mucosal IgG and IgA, as well as cellular responses dominated by type 1/type 17 cytokine profiles. All mice vaccinated with the [N-3M2e + N-LAH + MG] formulation survived an H1N1 challenge and the combination of both N-3M2e and N-LAH nanorings with MG enhanced the clinical and/or virological protective potential of the preparation in comparison to individual nanorings. Chickens vaccinated parenterally or mucosally with N-LAH and N-3M2e nanorings admixed with Montanide™ adjuvants developed a specific systemic humoral response, which nonetheless failed to confer protection against heterosubtypic challenge with a highly pathogenic H5N8 strain. Thus, while the combination of N-LAH and N-3M2e nanorings with Montanide™ adjuvants shows promise as a universal mucosal anti-IAV vaccine in the mouse model, further experiments have to be conducted to extend its efficacy to poultry. |
| format |
article |
| author |
Cynthia Calzas Molida Mao Mathilde Turpaud Quentin Viboud Joelle Mettier Thomas Figueroa Pierre Bessière Antoine Mangin Antoine Mangin Laura Sedano Pierre-Louis Hervé Pierre-Louis Hervé Romain Volmer Mariette F. Ducatez Steve Bourgault Denis Archambault Ronan Le Goffic Christophe Chevalier |
| author_facet |
Cynthia Calzas Molida Mao Mathilde Turpaud Quentin Viboud Joelle Mettier Thomas Figueroa Pierre Bessière Antoine Mangin Antoine Mangin Laura Sedano Pierre-Louis Hervé Pierre-Louis Hervé Romain Volmer Mariette F. Ducatez Steve Bourgault Denis Archambault Ronan Le Goffic Christophe Chevalier |
| author_sort |
Cynthia Calzas |
| title |
Immunogenicity and Protective Potential of Mucosal Vaccine Formulations Based on Conserved Epitopes of Influenza A Viruses Fused to an Innovative Ring Nanoplatform in Mice and Chickens |
| title_short |
Immunogenicity and Protective Potential of Mucosal Vaccine Formulations Based on Conserved Epitopes of Influenza A Viruses Fused to an Innovative Ring Nanoplatform in Mice and Chickens |
| title_full |
Immunogenicity and Protective Potential of Mucosal Vaccine Formulations Based on Conserved Epitopes of Influenza A Viruses Fused to an Innovative Ring Nanoplatform in Mice and Chickens |
| title_fullStr |
Immunogenicity and Protective Potential of Mucosal Vaccine Formulations Based on Conserved Epitopes of Influenza A Viruses Fused to an Innovative Ring Nanoplatform in Mice and Chickens |
| title_full_unstemmed |
Immunogenicity and Protective Potential of Mucosal Vaccine Formulations Based on Conserved Epitopes of Influenza A Viruses Fused to an Innovative Ring Nanoplatform in Mice and Chickens |
| title_sort |
immunogenicity and protective potential of mucosal vaccine formulations based on conserved epitopes of influenza a viruses fused to an innovative ring nanoplatform in mice and chickens |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/ce5eeb8fd4fc4f3c89ecec190951fa7b |
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