Use of an Attenuated Leishmanial Parasite as an Immunoprophylactic and Immunotherapeutic Agent against Murine Visceral Leishmaniasis

Abstract

The ability of the leishmanial parasite UR6 to act as an immunoprophylactic and immunotherapeutic agent against Leishmania donovani infection in BALB/c mice was investigated. Unlike the virulent L. donovani AG83 (MOHOM/IN/1983/AG83), UR6 given through intracardiac route failed to induce visceral infection, but when it was injected subcutaneously, UR6 induced a short-lived and localized self-healing skin lesion. Priming of peritoneal macrophages with UR6 in vitro induced superoxide (O 2 ؊ ) generation, whereas similar experiments with virulent AG83 inhibited O 2 ؊ generation. It was observed that priming of mice with either live or sonicated UR6 in the absence of any adjuvant provided strong protection against subsequent virulent challenge. Further, UR6-primed infected mice not only displayed a strong antileishmanial delayed-type hypersensitivity (DTH) response but also showed an elevated level of the serum antileishmanial immunoglobulin G2a (IgG2a) isotype, whereas infected mice failed to mount any antileishmanial DTH response and showed an elevated level of IgG1. This indicates that UR6 priming and subsequent L. donovani infection allowed the expansion of Th1 cells. Our studies indicate that UR6 has potential to be used as an immunoprophylactic and immunotherapeutic agent against experimental visceral leishmaniasis.

Vaccination Route That Induces Transforming Growth Factor β Production Fails To Elicit Protective Immunity againstLeishmania donovaniInfection

“…The outcomes of challenge infections in BALB/c mice following vaccination via four different routes with LAg and LAg in liposomes were evaluated. In contrast to selflimiting infection (26,29), inoculation of BALB/c mice with L. donovani strain AG83 leads to progressive infection in the liver and spleen, corresponding with hepato-and splenomegaly (2,7,19,24). Figure 1A shows that mice vaccinated with LAg through the i.p.…”

Leishmaniasis treatment—a challenge that remains: a review

“…The development of vaccines against leishmaniasis is directly related to host immunity and to the development of immunity after the patient healing from VL or CL (Mukhopadhyay et al 2000). Based on attenuated, dead, or ruptured parasites, isolation and purification of antigens, and parasites encapsulated in liposomes, this process has been widely investigated (Soong et al 1995;Mukhopadhyay et al 2000).…”

“…Based on attenuated, dead, or ruptured parasites, isolation and purification of antigens, and parasites encapsulated in liposomes, this process has been widely investigated (Soong et al 1995;Mukhopadhyay et al 2000). Soong et al (1995) isolated antigens P4 and P8 from L. pifanoi amastigotes and used them to immunize infected mice.…”

Hybrid Cell Vaccination ResolvesLeishmania donovaniInfection by Eliciting a Strong CD8+Cytotoxic T-Lymphocyte Response with Concomitant Suppression of Interleukin-10 (IL-10) but Not IL-4 or IL-13

“…The virulent L. donovani strain AG83 (MHOM/IN/1983/AG83) used in the present study kinetics of infection different from that of the Sudanese (LV9 and LV82) and Ethiopian strains of L. donovani used in other studies (28,40). After AG83 challenge, an exponential rise in both the splenic and the hepatic parasite burdens occurs until 5 months postinfection in a BALB/c mice model (29,4). Since a cure from late-stage infection, at which the reversal of immune dysregulation is most critical, is the most desirable indicator of immunotherapeutic efficacy, we tried HCV therapy in a BALB/c mouse model at 60 days postinfection.…”