6th International Influenza Meeting

Cross-protective potential and protection-relevant immune mechanisms of whole inactivated influenza virus vaccines are determined by adjuvants and route of immunization

Not scheduled

15m

Oral presentation

Description

Adjuvanted whole inactivated virus (WIV) influenza vaccines show promise as universal 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/PR/8/34 (H1N1) virus administered 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 anti-viral serum IgG, mucosal IgA and splenic IFNγ-producing CD4 T cells. As a result, intranasal immunizations with adjuvanted vaccines afforded strong cross-protection associated with less clinical symptoms and control of lung viral load. 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 best cross-protection was stimulated by CAF09 and CTA1-3M2e-DD, with the latter also providing CD4 T cell-dependent reduction of lung virus titers. Thus, intranasally administered WIV in combination with effective mucosal adjuvants appears to be a promising candidate for a broadly protective influenza vaccine.