Vaccination with Leishmania Hemoglobin Receptor–Encoding DNA Protects Against Visceral Leishmaniasis

Abstract

Leishmaniasis is a severe infectious disease. Drugs used for leishmaniasis are very toxic, and no vaccine is available. We found that the hemoglobin receptor (HbR) of Leishmania was conserved across various strains of Leishmania, and anti-HbR antibody could be detected in kala-azar patients' sera. Our results showed that immunization with HbR-DNA induces complete protection against virulent Leishmania donovani infection in both BALB/c mice and hamsters. Moreover, HbR-DNA immunization stimulated the production of protective cytokines like interferon-γ (IFN-γ), interleukin-12 (IL-12), and tumor necrosis factor-α (TNF-α) with concomitant down-regulation of disease-promoting cytokines like IL-10 and IL-4. HbR-DNA vaccination also induced a protective response by generating multifunctional CD4(+) and CD8(+) T cells. All HbR-DNA-vaccinated hamsters showed sterile protection and survived during an experimental period of 8 months. These findings demonstrate the potential of HbR as a vaccine candidate against visceral leishmaniasis.

GTPase Sar1 regulates the trafficking and secretion of the virulence factor gp63 in Leishmania

“…Recently, we have shown that Ldgp63 is trafficked via Rab1 dependent conventional secretory pathway in Leishmania (36). Moreover, we have also shown that Leishmania has conserved trafficking pathways like higher eukaryotic cells (37)(38)(39)(40)(41)(42)(43)(44). Thus, it is tempting to speculate that Ldgp63 might exit from ER by Sar1-dependent COPII mediated process.…”

Rab5 Isoforms Specifically Regulate Different Modes of Endocytosis in Leishmania

“…Moreover, depletion, overexpression, or generation of the null-mutant of target gene/protein shows the phenotype and affects the viability of the cells and thereby indicates the essential functions of the respective Rabs in an organism. Previously, we have shown that Hb endocytosis is a clathrin-mediated process in Leishmania (23)(24)(25) and is essential for parasite survival (40). Therefore, we have used Hb as a receptor-mediated endocytic probe and ϩ/Ϫ , and Leishmania:Rab5b ϩ/Ϫ .…”

A Targeted and Adjuvanted Nanoparticle for Immunochemotherapy of Leishmania Infections

“…Importantly, protective immunity against these obligatory intracellular parasites requires T-helper 1 (Th1 type) cellular immune responses, including interferon (IFN)-γ-secreting CD4 T cells and cytotoxic CD8 T cells [1,3]. To blunt the generation of protective immunity, leishmania parasites use immune-avoidance mechanisms, including changes in interleukin (IL)-10 expression [4].…”