title: Development and pre-clinical assessment of a 73 kD chimeric fusion protein as a defined sub-unit vaccine for leprosy.
abstract: 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.
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98104, USA. mduthie@idri.org
authors.forename: Malcolm S
authors.initials: MS
authors.lastname: Duthie
authors.forename: Lucas H
authors.initials: LH
authors.lastname: Sampaio
authors.forename: Regiane M
authors.initials: RM
authors.lastname: Oliveira
authors.forename: Vanitha S
authors.initials: VS
authors.lastname: Raman
authors.forename: Joanne
authors.initials: J
authors.lastname: O'Donnell
authors.forename: H Remy
authors.initials: HR
authors.lastname: Bailor
authors.forename: Greg C
authors.initials: GC
authors.lastname: Ireton
authors.forename: Ana Lucia M
authors.initials: AL
authors.lastname: Sousa
authors.forename: Mariane M A
authors.initials: MM
authors.lastname: Stefani
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D007918:Leprosy / Q000276:immunology / Q000517:prevention & control*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009166:Mycobacterium leprae / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D007371:Interferon-gamma