Antileprosy vaccine; an apprehension
To the Editor:
Leprosy or Hansen's disease is a chronic disease resulting from infection with Mycobacterium leprae . Variation in host immune responses to M. leprae results in a spectrum of clinical manifestations (7). At one end of the spectrum is tuberculoid leprosy in which lesions are paucibacillary and cell-mediated immunity is essentially normal. At the opposite end is the lepromatous form of the disease in which monocytes/ macrophages are packed with viable M. leprae and cellular immunity to M. leprae is poor. Since leprosy is a great health problem for tropical and subtropical countries, the development of vaccine(s) for control of this disease has been one of the favorite choices and has attracted a great deal of attention for many years. Although several candidate vaccines have been claimed (1, 2) no approved vaccine is available to date for immunoprophylactic use in the population. The trial studies for some of the vaccines have demonstrated varying levels of protection against leprosy. In the present communication, I have discussed a possible apprehension about the protective efhcacy of an antileprosy vaccine.
Generally, most individuals who are infected with M. leprae develop protective immunity and do not show clinical symptoms. However, individuals who contract the disease have either the lepromatous or the tuberculoid type. The reasons for these varied forms of the disease are not know so far. Nonetheless, it is now well understood that protective immunity against M. leprae is provided by cell-mediated immunity (CMI) (5, 9) in which T cells play a major role. For induction of CMI, the T cells require that the antigen is processed and presented by antigen-presenting cells (11). This involves the internalization of the antigens into an acidic compartment, proteolytic degradation of the antigen, and binding of the resulting antigenic peptide fragments to the MHC molecules. M. leprae is known to parasitize macrophages (the main antigenpresenting cells), principally in lepromatous leprosy (6, 8 ). Studies on the interaction between M. leprae and macrophages have shown that following M. leprae infection macrophages fail in inducing the M. leprae degrading mechanisms (4, l0), a prerequisite for antigen processing and presentation. The molecular biology of these defects is as yet obscure. In addition to this, Hirschberg (3) has reported that patients with lepromatous leprosy are unable to exert a cell-mediated immune response due to the failure of their macrophages to present M. leprae antigens in an immunogenic form. Thus, all of the foregoing information raises intriguing questions as to the success of an antileprosy vaccine.
An ideal vaccine elicits protective immunity and memory so that subsequent exposure to the respective pathogen will result in an immune response of a protective nature. For stimulation of memory, T cells (generated after vaccination) and bacterial antigens need to be processed and presented by antigen-presenting cells. Using candidate vaccines against leprosy it may be feasible to generate the memory cells to provide protection against M. leprae infection. However, I wish to suggest that perhaps lepromatous leprosy-prone individuals, whose antigen-presenting cells are not capable of killing M. leprae and presenting M. leprae antigen(s), might present no/insufficient antigen(s) after M. leprae infection to stimulate the memory T cells. If this is so, then it is worth arguing that probably for such persons an antileprosy vaccine may not be successful in providing protective immunity. Contrary to this, tuberculoid leprosyprone individuals, whose antigen-presenting cells are capable of killing M. leprae and presenting the M. leprae antigen(s), could be made immune against M. leprae infection.
- Om Parkash, Ph.D.
Research Officer (Immunology)
Central JALMA Institute for Leprosy
P. O. Box 31, Taj Gary
Agra 282001, India.
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