Cross-Protective Potential and Protection-Relevant Immune Mechanisms of Whole Inactivated Influenza Virus Vaccines Are Determined by Adjuvants and Route of Immunization

Bhide, Y., Dong, W., Gribonika, I., Voshart, D., Meijerhof, T., de Vries-Idema, J., Norley, S., Guilfoyle, K., Skeldon, S., Engelhardt, O. G., Boon, L., Christensen, D., Lycke, N. & Huckriede, A., 29-Mar-2019, In : Frontiers in Immunology. 10, 13 p., 646.

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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 (RINI) 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-IgG, and splenic IFN gamma-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.

Original languageEnglish
Article number646
Number of pages13
JournalFrontiers in Immunology
Publication statusPublished - 29-Mar-2019


  • whole inactivated virus (WIV) influenza vaccines, liposome-based adjuvants, protein-based adjuvants, cross protection, non-neutralizing serum antibodies, CD4 T cells, T-CELL RESPONSES, HETEROSUBTYPIC IMMUNITY, PULMONARY DELIVERY, SUBUNIT VACCINE, INFECTION, ANTIBODY, MICE, INDUCTION, CTA1-DD, ANTIGEN

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