Phosphatidylinositol di-mannoside and derivates modulate the immune response to and efficacy of a tuberculosis protein vaccine against Mycobacterium bovis infection.

Mycobacterium bovis infects a wide range of hosts, including domestic livestock, wildlife, and humans. Development of an effective vaccine protecting against bovine tuberculosis would provide a cost-effective tuberculosis control strategy. The objective of this study was to investigate the ability of phosphatidylinositol di-mannoside (PIM(2)) and its derivatives to modulate cell-mediated immunity in vivo in a bovine tuberculosis mouse model in response to a relevant antigen, namely a fusion protein of mycobacterial proteins Ag85A and ESAT-6. The addition of synthetic PIM(2) to the vaccine resulted in a significant reduction in lung bacterial counts and a cytokine profile indicating a Th 1 type immune response. The addition of the other PIM(2) derivatives to the vaccine or the fusion protein alone did not result in reduced lung bacterial counts; moreover, the addition of PIM(2)ME appeared to negate the induction of an antigen-specific interferon-γ response and protection against tuberculosis. In conclusion, this study provides further evidence that PIMs can function as potent adjuvants for protein or sub-unit vaccines, but subtle structural differences among PIMs can markedly alter the type of immune response induced.