Immunity and mycobacterial infection : new generation vaccines for leprosy

Abstract

One of the greatest triumphs of medical science has been the development of vaccines that provide protective immunity from infectious diseases. These vaccines have been based on the isolation of the infectious agent and the subsequent inactivation or attenuation of the agent for use in immunization to yield immune responses of a protective nature. There are a number of diseases where this approach has led to immune responses but not to the development of protective immunity. These include a range of tropical diseases caused by protozoan parasites. leprosy, tuberculosis and AIDS. In developing a vaccine for leprosy there appear to be three relevant arguments to consider. First, most individuals who are infected with Mycobacterium leprae develop protective immunity and do not get clinical disease. Second, it is apparent that the clinical spectrum of disease can be correlated with cell-mediated immune responses to M.leprae. Third, while these observations are indicative that, in susceptible individuals, the immune response to M.leprae has a dramatic effect on the clinical spectrum of the disease, they do not throw light on the immunological difference between individuals that develop leprosy and those who are infected but develop protective immunity. Analyses of recombinant proteins isolated from genomic libraries of M.leprae have yielded chemically-defined new immunologically-reactive epitopes. These epitopes are peptides which are produced by degradation of bacterial proteins in antigen-presenting cells. The peptides which represent the epitopes associate with newly synthesized class II molecules of the major histocompatibility complex. I will describe our analysis of the 18kD protein antigen of Mycobacterium leprae and discuss ways that peptide fragments may be engineered into new vaccines and presented to individuals for immunization. The immunological basis of protective immunity will be reviewed. One of the greatest triumphs of medical science has been the development of vaccines that provide protective immunity from infectious diseases. These vaccines have been based on the isolation of the infectious agent and the subsequent inactivation or attenuation of the agent for use in immunization to yield immune responses of a protective nature. There are a number of diseases where this approach has led to immune responses but not to the development of protective immunity. These include a range of tropical diseases caused by protozoan parasites. leprosy, tuberculosis and AIDS. In developing a vaccine for leprosy there appear to be three relevant arguments to consider. First, most individuals who are infected with Mycobacterium leprae develop protective immunity and do not get clinical disease. Second, it is apparent that the clinical spectrum of disease can be correlated with cell-mediated immune responses to M.leprae. Third, while these observations are indicative that, in susceptible individuals, the immune response to M.leprae has a dramatic effect on the clinical spectrum of the disease, they do not throw light on the immunological difference between individuals that develop leprosy and those who are infected but develop protective immunity. Analyses of recombinant proteins isolated from genomic libraries of M.leprae have yielded chemically-defined new immunologically-reactive epitopes. These epitopes are peptides which are produced by degradation of bacterial proteins in antigen-presenting cells. The peptides which represent the epitopes associate with newly synthesized class II molecules of the major histocompatibility complex. I will describe our analysis of the 18kD protein antigen of Mycobacterium leprae and discuss ways that peptide fragments may be engineered into new vaccines and presented to individuals for immunization. The immunological basis of protective immunity will be reviewed.