Lund University Publications

@article{5680dfc1-1adf-4ce9-a7f1-70bf15515337,
  abstract     = {{<p>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.</p>}},
  author       = {{Bhide, Yoshita and Dong, Wei and Gribonika, Inta and Voshart, Daniëlle and Meijerhof, Tjarko and de Vries-Idema, Jacqueline and Norley, Stephen and Guilfoyle, Kate and Skeldon, Sarah and Engelhardt, Othmar G and Boon, Louis and Christensen, Dennis and Lycke, Nils and Huckriede, Anke}},
  issn         = {{1664-3224}},
  keywords     = {{Adjuvants, Immunologic/chemistry; Administration, Intranasal; Animals; Antibodies, Neutralizing/immunology; Antibodies, Viral/immunology; CD4-Positive T-Lymphocytes/immunology; Cross Protection; Female; Immunoglobulin G/immunology; Influenza A Virus, H1N1 Subtype/immunology; Influenza A Virus, H3N2 Subtype/immunology; Influenza Vaccines/chemistry; Mice; Mice, Inbred BALB C; Orthomyxoviridae Infections/immunology; Vaccines, Inactivated/chemistry}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Immunology}},
  title        = {{Cross-Protective Potential and Protection-Relevant Immune Mechanisms of Whole Inactivated Influenza Virus Vaccines Are Determined by Adjuvants and Route of Immunization}},
  url          = {{http://dx.doi.org/10.3389/fimmu.2019.00646}},
  doi          = {{10.3389/fimmu.2019.00646}},
  volume       = {{10}},
  year         = {{2019}},
}