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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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Autores principales: Calzas, Cynthia, Mao, Molida, Turpaud, Mathilde, Viboud, Quentin, Mettier, Joelle, Figueroa, Thomas, Bessière, Pierre, Mangin, Antoine, Sedano, Laura, Hervé, Pierre-Louis, Volmer, Romain, Ducatez, Mariette F., Bourgault, Steve, Archambault, Denis, Le Goffic, Ronan, Chevalier, Christophe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632632/
https://www.ncbi.nlm.nih.gov/pubmed/34868036
http://dx.doi.org/10.3389/fimmu.2021.772550
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author Calzas, Cynthia
Mao, Molida
Turpaud, Mathilde
Viboud, Quentin
Mettier, Joelle
Figueroa, Thomas
Bessière, Pierre
Mangin, Antoine
Sedano, Laura
Hervé, Pierre-Louis
Volmer, Romain
Ducatez, Mariette F.
Bourgault, Steve
Archambault, Denis
Le Goffic, Ronan
Chevalier, Christophe
author_facet Calzas, Cynthia
Mao, Molida
Turpaud, Mathilde
Viboud, Quentin
Mettier, Joelle
Figueroa, Thomas
Bessière, Pierre
Mangin, Antoine
Sedano, Laura
Hervé, Pierre-Louis
Volmer, Romain
Ducatez, Mariette F.
Bourgault, Steve
Archambault, Denis
Le Goffic, Ronan
Chevalier, Christophe
author_sort Calzas, Cynthia
collection PubMed
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.
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spelling pubmed-86326322021-12-02 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 Calzas, Cynthia Mao, Molida Turpaud, Mathilde Viboud, Quentin Mettier, Joelle Figueroa, Thomas Bessière, Pierre Mangin, Antoine Sedano, Laura Hervé, Pierre-Louis Volmer, Romain Ducatez, Mariette F. Bourgault, Steve Archambault, Denis Le Goffic, Ronan Chevalier, Christophe Front Immunol Immunology 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. Frontiers Media S.A. 2021-11-11 /pmc/articles/PMC8632632/ /pubmed/34868036 http://dx.doi.org/10.3389/fimmu.2021.772550 Text en Copyright © 2021 Calzas, Mao, Turpaud, Viboud, Mettier, Figueroa, Bessière, Mangin, Sedano, Hervé, Volmer, Ducatez, Bourgault, Archambault, Le Goffic and Chevalier https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Calzas, Cynthia
Mao, Molida
Turpaud, Mathilde
Viboud, Quentin
Mettier, Joelle
Figueroa, Thomas
Bessière, Pierre
Mangin, Antoine
Sedano, Laura
Hervé, Pierre-Louis
Volmer, Romain
Ducatez, Mariette F.
Bourgault, Steve
Archambault, Denis
Le Goffic, Ronan
Chevalier, Christophe
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 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_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_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
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632632/
https://www.ncbi.nlm.nih.gov/pubmed/34868036
http://dx.doi.org/10.3389/fimmu.2021.772550
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