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Immune recognition of a novel 45kDa antigen, specific to Mycobacterium leprae, and evaluation as a potential vaccine candidate

Objective



THE SEOUENCE OF THE GENE FOR THE M.LEPRAE SERINE-RICH ANTIGEN HAS RECENTLY BEEN PUBLISHED INDEPENTLY BY THE GROUPS COLLABORATING IN THIS APPLICATION. THIS M.LEPRAE-SPECIFIC ANTIGEN IS OF PARTICULAR INTEREST, AS IT MAY PROVIDE THE FIRST TOOL WITH WHICH M.LEPRAESPECIFIC T CELL RESPONSES CAN BE ANALYSED IN LEPROSY ENDEMIC POPULATIONS.

THE PROJECT WILL GENERATE A PANEL OF REAGENTS, INCLUDING PURIFIED RECOMBINANT ANTIGEN AND SYNTHETIC PEPTIDES SPANNING ITS LENGTH, WITH WHICH IMMUNE RESPONSES CAN BE ANALYSED.
THESE REAGENTS WILL THEN BE USED IN IN VITRO ASSAYS TO MEASURE T CELL PROLIFERATION AND CYTOKINE SECRETION, USING PERIPHERAL BLOOD MONONUCLEAR CELLS FROM LEPROSY PATIENTS AND ENDEMIC CONTROLS IN MEXICO.
THESE STUDIES WILL REVEAL WHETHER TUBERCULOID LEPROSY PATIENTS MOUNT A STRONG T CELL RESPONSE TO THIS ANTIGEN, AND WHETHER RESPONSES ARE ALSO PRESENT IN HEALTHY LEPROSY CONTACTS OR ENDEMIC CONTROLS.
THE CYTOKINE STUDIES WILL ASSESS WHETHER THE 45KDA ANTIGEN TRIGGERS A PREDOMINANTLY THl T CELL RESPONSE, WHICH MIGHT BE PROTECTIVE, OR TH2 AND MACROPHAGE CYTOKINES, WHICH MIGHT CAUSE IMMUNOSUPPRESSION OR IMMUNOPATHOLOGY.

A NEW WHOLE BLOOD ASSAY WILL ALLOW AN IMMUNOEPIDEMIOLOGICAL ANALYSIS OF CYTOKINE RESPONSES IN THE FIELD.
FURTHER STUDIES USING T CELL CLONES WILL DEFINE THE EPITOPES RECOGNISED WITHIN THE 45KDA PROTEIN.
AS PRELIMINARY RESULTS HAVE SHoWN STRONG ANTIBODY RESPONSES TO THE 45KDA ANTIGEN IN LEPROSY PATIENTS WITH A HISTORY OF ENL, PATIENTS WITH ENL REACTIONS WILL BE TESTED FOR IMMWNE RECOGNITION OF THE 45KDA ANTIGEN, AND A PROSPECTIVE STUDY SET UP TO ASSESS THE VALUE OF IMMUNE RESPONSES TO THIS PROTEIN IN THE PREDICTION OF REACTIONAL EPISODES.
ULTIMATELY THIS ANTIGEN MAY PROVIDE A USEFUL TOOL FOR MONITORING SUBCLINICAL OR EARLY INFECTIONS WITH M.LEPRAE, AS WELL AS BEING A CANDIDATE ANTIGEN FOR INCLUSION IN A NEW RATIONAL VACCINE AGAINST LEPROSY.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

London School of Hygiene and TropicalMedicine
Address
Keppel Street
WC1E 7HT London
United Kingdom

Participants (2)

Instituto Mexicano del Seguro Social
Mexico
Address
330,Cuatchemoc
06725 Mexico City
Rijksuniversiteit Leiden
Netherlands
Address
10,Rijnsburgerweg
2300 RC Leiden