Adjuvanticity of a Synthetic Phosphatidylinositol Dimannoside to a Subvirion Influenza Vaccine in an Influenza Mouse Model

Tao Zheng, Dongwen Luo, Benjamin J Compton, Gavin F Painter, Maurice R Alley, David S Larsen, Bryce M Buddle and Axel Heiser

Dose-sparing is one of the key strategies to rapidly develop and supply vaccines to combat emerging strains of influenza virus. The objective of this study was to evaluate the adjuvanticity of a synthetic phosphatidylinositol dimannoside (PIM2) and/or aluminium hydroxide to a subvirion influenza vaccine (APR8). Mice were immunised with a suboptimal dose vaccine alone or formulated with PIM2, aluminium hydroxide or the two combined. Immunised mice were challenged with a lethal dose APR8 virus. PIM2 significantly enhanced virus-specific T cell cytotoxicity and immunised mice had significantly reduced pulmonary virus load. Aluminium hydroxide adjuvant significantly boosted virus-specific humoral and cellular responses and conferred improved protection in mice against a lethal challenge. The magnitude of enhanced immune responses and protection by the addition of aluminium hydroxide to the vaccine was over 10-fold more. Aluminium hydroxide conferred stronger adjuvanticity to the vaccine compared to PIM2. The adjuvanticity of aluminium hydroxide was further augmented in combination with PIM2 boosting virus-specific T cell cytotoxicity and resulting in a significantly lower lung virus load compared to that for vaccine containing a 10-fold higher antigen dose. The addition of adjuvants to an influenza vaccine could substantially lower the antigen doses required and more doses of efficacious influenza vaccine would be produced with limited antigen supply, such as in the early phase of an influenza pandemic.