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

TitlePhosphatidylinositol di-mannoside and derivates modulate the immune response to and efficacy of a tuberculosis protein vaccine against Mycobacterium bovis infection
Publication TypeJournal Article
Year of Publication2012
AuthorsParlane, N. A., Compton B. J., Hayman C. M., Painter G. F., Basaraba R. J., Heiser A., and Buddle B. M.
IRL TeamCarbohydrate Chemistry
JournalVaccine
Volume30
Pagination580-588
ISSN0264410X
Abstract 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. © 2011 Elsevier Ltd.
URLhttp://www.scopus.com/inward/record.url?eid=2-s2.0-84355166213&partnerID=40&md5=d96c28a54abad25850c30f337774eda4
DOI10.1016/j.vaccine.2011.11.055