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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00646/full |
| _version_ | 1818597594202374144 |
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| author | Yoshita Bhide Wei Dong Inta Gribonika Daniëlle Voshart Tjarko Meijerhof Jacqueline de Vries-Idema Stephen Norley Kate Guilfoyle Sarah Skeldon Othmar G. Engelhardt Louis Boon Dennis Christensen Nils Lycke Anke Huckriede |
| author_facet | Yoshita Bhide Wei Dong Inta Gribonika Daniëlle Voshart Tjarko Meijerhof Jacqueline de Vries-Idema Stephen Norley Kate Guilfoyle Sarah Skeldon Othmar G. Engelhardt Louis Boon Dennis Christensen Nils Lycke Anke Huckriede |
| author_sort | Yoshita Bhide |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-16T11:50:17Z |
| format | Article |
| id | doaj.art-87556b2c48d6402581080a16c5962737 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-16T11:50:17Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-87556b2c48d6402581080a16c59627372022-12-21T22:32:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-03-011010.3389/fimmu.2019.00646427274Cross-Protective Potential and Protection-Relevant Immune Mechanisms of Whole Inactivated Influenza Virus Vaccines Are Determined by Adjuvants and Route of ImmunizationYoshita Bhide0Wei Dong1Inta Gribonika2Daniëlle Voshart3Tjarko Meijerhof4Jacqueline de Vries-Idema5Stephen Norley6Kate Guilfoyle7Sarah Skeldon8Othmar G. Engelhardt9Louis Boon10Dennis Christensen11Nils Lycke12Anke Huckriede13Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Microbiology and Immunology, Institute of Biomedicine, Gothenburg University, Gothenburg, SwedenDepartment of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Infectious Diseases, Robert Koch Institute, Berlin, GermanyDivision of Virology, National Institute for Biological Standards and Control (NIBSC), Medicines and Healthcare products Regulatory Agency (MHRA), Potters Bar, United KingdomDivision of Virology, National Institute for Biological Standards and Control (NIBSC), Medicines and Healthcare products Regulatory Agency (MHRA), Potters Bar, United KingdomDivision of Virology, National Institute for Biological Standards and Control (NIBSC), Medicines and Healthcare products Regulatory Agency (MHRA), Potters Bar, United KingdomBioceros, Utrecht, NetherlandsAdjuvant Research, Department of Infectious Diseases Immunology, Statens Serum Institut (SSI), Copenhagen, DenmarkDepartment of Microbiology and Immunology, Institute of Biomedicine, Gothenburg University, Gothenburg, SwedenDepartment of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsAdjuvanted 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.00646/fullwhole inactivated virus (WIV) influenza vaccinesliposome-based adjuvantsprotein-based adjuvantscross protectionnon-neutralizing serum antibodiesCD4 T cells |
| spellingShingle | Yoshita Bhide Wei Dong Inta Gribonika Daniëlle Voshart Tjarko Meijerhof Jacqueline de Vries-Idema Stephen Norley Kate Guilfoyle Sarah Skeldon Othmar G. Engelhardt Louis Boon Dennis Christensen Nils Lycke Anke Huckriede Cross-Protective Potential and Protection-Relevant Immune Mechanisms of Whole Inactivated Influenza Virus Vaccines Are Determined by Adjuvants and Route of Immunization Frontiers in Immunology whole inactivated virus (WIV) influenza vaccines liposome-based adjuvants protein-based adjuvants cross protection non-neutralizing serum antibodies CD4 T cells |
| 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 | whole inactivated virus (WIV) influenza vaccines liposome-based adjuvants protein-based adjuvants cross protection non-neutralizing serum antibodies CD4 T cells |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.00646/full |
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