02536nas a2200529   4500000000100000008004100001260001600042653002700058653001500085653001000100653000900110653002200119653001200141653002600153653002400179653002300203653001100226653001100237653002100248653002100269653001200290653002800302653000900330653000900339653002300348653001600371653002500387653003200412653001400444653002400458653001600482100001300498700001500511700001600526700001300542700001600555700001400571700001300585700001300598700001400611700001100625245012200636300001000758490000700768520121700775022001401992       2013                            d  c2013 Jan 2110aAdjuvants, Immunologic10aAdolescent10aAdult10aAged10aAged, 80 and over10aAnimals10aAntibodies, Bacterial10aAntigens, Bacterial10aBacterial Vaccines10aFemale10aHumans10aImmunoglobulin G10aInterferon-gamma10aleprosy10aLeukocytes, Mononuclear10aMale10aMice10aMice, Inbred C57BL10aMiddle Aged10aMycobacterium leprae10aRecombinant Fusion Proteins10aTh1 Cells10aVaccines, Synthetic10aYoung Adult1 aDuthie M1 aSampaio LS1 aOliveira RM1 aRaman VS1 aO'Donnell J1 aBailor RH1 aIreton G1 aSousa AL1 aStefani M1 aReed S00aDevelopment and pre-clinical assessment of a 73 kD chimeric fusion protein as a defined sub-unit vaccine for leprosy.  a813-90 v313 a<p>Despite the advances toward the elimination of leprosy through widespread provision of multi-drug therapy to registered patients over the last 2 decades, new case detection rates have stabilized and leprosy remains endemic in a number of localized regions. A vaccine could overcome the inherent limitations of the drug treatment program by providing protection in individuals who are not already harboring the Mycobacterium leprae bacilli at the time of administration and effectively interrupt the transmission cycle over a wider timespan. In this report we present data validating the production of 73f, a chimeric fusion protein incorporating the M. leprae antigens ML2028, ML2346 and ML2044. The 73f protein was recognized by IgG in multibacillary (MB) leprosy patient sera and stimulated IFNγ production within whole blood assays of paucibacillary (PB) leprosy patient and healthy household contacts of MB patients (HHC). When formulated with a TLR4L-containing adjuvant (GLA-SE), 73f stimulated a strong and pluripotent Th1 response that inhibited M. leprae-induced inflammation in mice. We are using these data to develop new vaccine initiatives for the continued and long-term control of leprosy.</p>  a1873-2518