CORRELATES OF IMMUNE PROTECTION AGAINST TB IN BCG VACCINATED NONHUMAN PRIMATES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We were initially funded to identify the transcriptome of BCG vaccinated macaques following infection with Mtb (SPID 0941). We identified a small, discrete group of genes whose expression was perturbed in a statistically significant manner, as a result of BCG vaccination. Immune function genes such as FoxP3, MIP, IL-6 and IL-24, which were expressed in both vaccinated and control groups, as well as IFN-gamma, IL-8, IL-21, IL-17, IL-27 and RANTES, which were specifically expressed, only in BCG vaccinated animal lungs. Our results clearly indicate that vaccination with BCG clearly and effectively modulates the immune system at the site of Mtb infection. Some of these changes may play a role in inducing localized protection from Mtb infection. These preliminary data helped us obtain cooperative seed funding ($75,000 per year total costs for a period of two years), from the Louisiana Board of Regents, through the Louisiana Vaccine Center (LVC)/South Louisiana Institute for Infectious Disease Research mechanism. Using samples from the TNPRC pilot, we looked at gene expression changes 8 months post Mtb infection. The LVC funds will allow us to look at short term (1-3 month post infection) changes in gene-expression as a function of Mtb infection and BCG vaccination, as the dynamics of the granuloma evolve. In addition to gene-expression in lung-granuloma's we will also study gene-expression and immune cell recruitment in peripheral blood and in Broncho-alveolar lavages of these animals. The animal experiment has recently been completed. These animals were assigned in Apr 2009, vaccinated with BCG in May 2009 and infected with Mtb in Sept 2009. All animals have been euthanized and samples collected. Data analysis is in progress.