Phosphatidylinositol di-mannoside and derivates modulate the immune response to and efficacy of a tuberculosis protein vaccine against Mycobacterium bovis infection
2012
Parlane, Natalie A. | Compton, Benjamin J. | Hayman, Colin M. | Painter, Gavin F. | Basaraba, Randall J. | Heiser, Axel | Buddle, Bryce M.
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 (PIM₂) 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 PIM₂ 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 PIM₂ derivatives to the vaccine or the fusion protein alone did not result in reduced lung bacterial counts; moreover, the addition of PIM₂ME 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.
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