02881nas a2200409   4500000000100000008004100001260001300042653002700055653001200082653002400094653002300118653002800141653001100169653001700180653002100197653001200218653000900230653002300239653002500262653001800287653002400305653002200329100001300351700001600364700001400380700001100394700001300405700001300418700001100431700001300442245014400455856007200599300001200671490000700683520176700690022001402457       2009                            d  c2009 Dec10aAdjuvants, Immunologic10aAnimals10aAntigens, Bacterial10aBacterial Vaccines10aColony Count, Microbial10aFemale10aInflammation10aInterferon-gamma10aleprosy10aMice10aMice, Inbred C57BL10aMycobacterium leprae10aT-Lymphocytes10aToll-Like Receptors10aVaccines, Subunit1 aRaman VS1 aO'Donnell J1 aBailor RH1 aGoto W1 aLahiri R1 aGillis T1 aReed S1 aDuthie M00aVaccination with the ML0276 antigen reduces local inflammation but not bacterial burden during experimental Mycobacterium leprae infection.  uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2786448/pdf/0508-09.pdf  a5623-300 v773 a<p>Leprosy elimination has been a goal of the WHO for the past 15 years. Widespread BCG vaccination and multidrug therapy have dramatically reduced worldwide leprosy prevalence, but new case detection rates have remained relatively constant. These data suggest that additional control strategies, such as a subunit vaccine, are required to block transmission and to improve leprosy control. We recently identified several Mycobacterium leprae antigens that stimulate gamma interferon (IFN-gamma) secretion upon incubation with blood from paucibacillary leprosy patients, a group who limit M. leprae growth and dissemination. In this study, we demonstrate that M. leprae-specific mouse T-cell lines recognize several of these antigens, with the ML0276 protein stimulating the most IFN-gamma secretion. We then examined if the ML0276 protein could be used in a subunit vaccine to provide protection against experimental M. leprae infection. Our data demonstrate that combining ML0276 with either a Toll-like receptor 4 (TLR4) (EM005), TLR7 (imiquimod), or TLR9 (CpG DNA) agonist during immunization induces Th1 responses that limit local inflammation upon experimental M. leprae infection. Our data indicate that only the ML0276/EM005 regimen is able to elicit a response that is transferable to recipient mice. Despite the potent Th1 response induced by this regimen, it could not provide protection in terms of limiting bacterial growth. We conclude that EM005 is the most potent adjuvant for stimulating a Th1 response and indicate that while a subunit vaccine containing the ML0276 protein may be useful for the prevention of immune pathology during leprosy, it will not control bacterial burden and is therefore unlikely to interrupt disease transmission.</p>  a1098-5522