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Cross-Protective Potential and Protection-Relevant Immune Mechanisms of Whole Inactivated Influenza Virus Vaccines Are Determined by Adjuvants and Route of Immunization
Adjuvanted whole inactivated virus (WIV) influenza vaccines show promise as broadly protective influenza vaccine candidates. Using WIV as basis we assessed the relative efficacy of different adjuvants by carrying out a head-to-head comparison of the liposome-based adjuvants CAF01 and CAF09 and the p...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450434/ https://www.ncbi.nlm.nih.gov/pubmed/30984200 http://dx.doi.org/10.3389/fimmu.2019.00646 |
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author | Bhide, Yoshita Dong, Wei Gribonika, Inta Voshart, Daniëlle Meijerhof, Tjarko de Vries-Idema, Jacqueline Norley, Stephen Guilfoyle, Kate Skeldon, Sarah Engelhardt, Othmar G. Boon, Louis Christensen, Dennis Lycke, Nils Huckriede, Anke |
author_facet | Bhide, Yoshita Dong, Wei Gribonika, Inta Voshart, Daniëlle Meijerhof, Tjarko de Vries-Idema, Jacqueline Norley, Stephen Guilfoyle, Kate Skeldon, Sarah Engelhardt, Othmar G. Boon, Louis Christensen, Dennis Lycke, Nils Huckriede, Anke |
author_sort | Bhide, Yoshita |
collection | PubMed |
description | Adjuvanted whole inactivated virus (WIV) influenza vaccines show promise as broadly protective influenza vaccine candidates. Using WIV as basis we assessed the relative efficacy of different adjuvants by carrying out a head-to-head comparison of the liposome-based adjuvants CAF01 and CAF09 and the protein-based adjuvants CTA1-DD and CTA1-3M2e-DD and evaluated whether one or more of the adjuvants could induce broadly protective immunity. Mice were immunized with WIV prepared from A/Puerto Rico/8/34 (H1N1) virus intramuscularly with or without CAF01 or intranasally with or without CAF09, CTA1-DD, or CTA1-3M2e-DD, followed by challenge with homologous, heterologous or heterosubtypic virus. In general, intranasal immunizations were significantly more effective than intramuscular immunizations in inducing virus-specific serum-IgG, mucosal-IgA, and splenic IFNγ-producing CD4 T cells. Intranasal immunizations with adjuvanted vaccines afforded strong cross-protection with milder clinical symptoms and better control of virus load in lungs. Mechanistic studies indicated that non-neutralizing IgG antibodies and CD4 T cells were responsible for the improved cross-protection while IgA antibodies were dispensable. The role of CD4 T cells was particularly pronounced for CTA1-3M2e-DD adjuvanted vaccine as evidenced by CD4 T cell-dependent reduction of lung virus titers and clinical symptoms. Thus, intranasally administered WIV in combination with effective mucosal adjuvants appears to be a promising broadly protective influenza vaccine candidate. |
format | Online Article Text |
id | pubmed-6450434 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64504342019-04-12 Cross-Protective Potential and Protection-Relevant Immune Mechanisms of Whole Inactivated Influenza Virus Vaccines Are Determined by Adjuvants and Route of Immunization Bhide, Yoshita Dong, Wei Gribonika, Inta Voshart, Daniëlle Meijerhof, Tjarko de Vries-Idema, Jacqueline Norley, Stephen Guilfoyle, Kate Skeldon, Sarah Engelhardt, Othmar G. Boon, Louis Christensen, Dennis Lycke, Nils Huckriede, Anke Front Immunol Immunology Adjuvanted whole inactivated virus (WIV) influenza vaccines show promise as broadly protective influenza vaccine candidates. Using WIV as basis we assessed the relative efficacy of different adjuvants by carrying out a head-to-head comparison of the liposome-based adjuvants CAF01 and CAF09 and the protein-based adjuvants CTA1-DD and CTA1-3M2e-DD and evaluated whether one or more of the adjuvants could induce broadly protective immunity. Mice were immunized with WIV prepared from A/Puerto Rico/8/34 (H1N1) virus intramuscularly with or without CAF01 or intranasally with or without CAF09, CTA1-DD, or CTA1-3M2e-DD, followed by challenge with homologous, heterologous or heterosubtypic virus. In general, intranasal immunizations were significantly more effective than intramuscular immunizations in inducing virus-specific serum-IgG, mucosal-IgA, and splenic IFNγ-producing CD4 T cells. Intranasal immunizations with adjuvanted vaccines afforded strong cross-protection with milder clinical symptoms and better control of virus load in lungs. Mechanistic studies indicated that non-neutralizing IgG antibodies and CD4 T cells were responsible for the improved cross-protection while IgA antibodies were dispensable. The role of CD4 T cells was particularly pronounced for CTA1-3M2e-DD adjuvanted vaccine as evidenced by CD4 T cell-dependent reduction of lung virus titers and clinical symptoms. Thus, intranasally administered WIV in combination with effective mucosal adjuvants appears to be a promising broadly protective influenza vaccine candidate. Frontiers Media S.A. 2019-03-29 /pmc/articles/PMC6450434/ /pubmed/30984200 http://dx.doi.org/10.3389/fimmu.2019.00646 Text en Copyright © 2019 Bhide, Dong, Gribonika, Voshart, Meijerhof, de Vries-Idema, Norley, Guilfoyle, Skeldon, Engelhardt, Boon, Christensen, Lycke and Huckriede. http://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 Bhide, Yoshita Dong, Wei Gribonika, Inta Voshart, Daniëlle Meijerhof, Tjarko de Vries-Idema, Jacqueline Norley, Stephen Guilfoyle, Kate Skeldon, Sarah Engelhardt, Othmar G. Boon, Louis Christensen, Dennis Lycke, Nils Huckriede, Anke Cross-Protective Potential and Protection-Relevant Immune Mechanisms of Whole Inactivated Influenza Virus Vaccines Are Determined by Adjuvants and Route of Immunization |
title | Cross-Protective Potential and Protection-Relevant Immune Mechanisms of Whole Inactivated Influenza Virus Vaccines Are Determined by Adjuvants and Route of Immunization |
title_full | Cross-Protective Potential and Protection-Relevant Immune Mechanisms of Whole Inactivated Influenza Virus Vaccines Are Determined by Adjuvants and Route of Immunization |
title_fullStr | Cross-Protective Potential and Protection-Relevant Immune Mechanisms of Whole Inactivated Influenza Virus Vaccines Are Determined by Adjuvants and Route of Immunization |
title_full_unstemmed | Cross-Protective Potential and Protection-Relevant Immune Mechanisms of Whole Inactivated Influenza Virus Vaccines Are Determined by Adjuvants and Route of Immunization |
title_short | Cross-Protective Potential and Protection-Relevant Immune Mechanisms of Whole Inactivated Influenza Virus Vaccines Are Determined by Adjuvants and Route of Immunization |
title_sort | cross-protective potential and protection-relevant immune mechanisms of whole inactivated influenza virus vaccines are determined by adjuvants and route of immunization |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450434/ https://www.ncbi.nlm.nih.gov/pubmed/30984200 http://dx.doi.org/10.3389/fimmu.2019.00646 |
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