Kala-azar: The immunological consequences and feasibility of vaccination Dube Anuradha, Srivastava Bindu Division of Parasitology, Central Drug Research Institute, P.B. 173, Lucknow - 226001, India. Abstract Among the various forms of leishmaniasis the Kala-azar caused by Leishmania donovani is the most fatal. The disease though localized in certain areas only, has gained significance because of high morality rate, particularly among children. The existing antileishmanial drugs are potentially toxic, having variable and poor success rate, especially in immunodepressed individuals, most notably in AIDS patients. Chemotherapeutic measures, alone are not sufficient to control and check the disease. As an alternate strategy, vaccination is under experimental and clinical trial. For the development of potential prophylactic/therapeutic measures, it is necessary to understand the immunological status of host during leishmaniasis. Active kala-azar disease is characterized by the marked elevation of humoral immune response i.e. by the production of plenty of specific as well as non-specific antibodies, but the antibodies so generated, have confered hardly any protection. The other most striking feature of Visceral leishmaniasis is severe impairment of cell mediated immune responses and therefore, the host is unable to combat several other opportunistic secondary infections like Tuberculosis and AIDS etc. Resistance and susceptibili ty to Leishmania sp. is mediated by Th I and Th2 subsets of CD4+ T-cells, respectively. Th 1 cells secrete protective cytokines IFN-γ (gammainterferon) an interluekin-2 (IL-2) and execute CMI responses (Delayed hypersenitivity and macrophage activation, where as Th2 cells produce disease exacerbative cytokines IL-4 and IL-10 and assist in antibody production for humoral immunity. First generation vaccine comprises killed leishmania parasites along with adjuvants viz. autoclaved L. major+ BCG which is under clinical trial against Cutaneous Leishmaniasis (CL) in Iran and 5udan yielding encouraging results. The same vaccine has shown potential against experimental viceral leishmaniasis (VL) also and is presently under clinical trial in Sudan. Taking lead from these approaches we evaluated autoclaved L. major (ALM) and autoclaved L donovani (ALD) preparations either alone or precipitated with alum in combination with BCG for vaccination in hamsters and Indian langurs (Presbytis entellus) against L. donovani infection. Alum-ALM or ALM+BCG vaccinated group of hamsters and lagnurs revealed almost complete protection. The depressed antibody and elevated CMI responses alos corroborated the protection. Based on above results, it appears that vaccination with first generation vaccines against VL is possible. Top Key words Leishmania donovani, Immunological responses, Live/killed/recombinant vaccines, immunnotherapy protective immunity. Top |