Amogh Anant Sahasrabuddhe

Visceral leishmaniasis (VL) is the third most severe infectious parasitic disease and is caused by the protozoan parasite Leishmania. To control the spread of the disease in endemic areas where the asymptomatic patients act as reservoirs as well as in nonendemic areas, an effective vaccine is indispensable. In this direction, we have developed three chimeric proteins by the combination of three already known Th1 stimulatory leishmanial antigens, i.e., enolase, aldolase, and triose phosphate isomerase (TPI). The newly developed chimeric proteins, i.e., enolase-aldolase, TPI-enolase, and aldolase-TPI along with BCG as an adjuvant were assessed and compared, examining humoral and cellular adaptive immune responses elicited in BALB/c mice. The three chimeric antigens exhibited differential immune responses shown by differences in Th1 and Th2 cytokine production in ex vivo stimulated splenocytes of immunized mice. It was observed that all three chimeric proteins are more immunogenic than their component proteins. However, while comparing the immune response of the three chimeric proteins, aldolase-TPI exhibited a better immunogenic (Th1-type) response, as evidenced by the highest IFN-gamma production, a high IgG2a antibody isotype switching, a high % population of CD8+ and CD4+ T-cells, and a significantly high expression of iNOS2. Thus, the results suggest the potential of these chimeric antigens as strong immunogens that can be harnessed in vaccine development against VL.

[This corrects the article DOI: 10.1371/journal.pone.0097911.].

Immunotherapy, a treatment based on host immune system activation, has been shown to provide a substitute for marginally effective conventional chemotherapy in controlling visceral leishmaniasis (VL), the deadliest form of leishmaniasis. As the majority of endemic inhabitants exhibit either subclinical or asymptomatic infection which often develops into the active disease state, therapeutic intervention seems to be an important avenue for combating infections by stimulating the natural defense system of infected individuals. With this perspective, the present study focuses on two immunodominant Leishmania (L.) donovani antigens (triosephosphate isomerase and enolase) previously proved to be potent prophylactic VL vaccine candidates, for generating a recombinant chimeric antigen. This is based on the premise that in a heterogeneous population, a multivalent antigen vaccine would be required for an effective response against leishmaniasis (a complex parasitic disease). The resulting molecule rLdT‐E chimeric protein was evaluated for its immunogenicity and immunotherapeutic efficacy. A Th1 stimulating adjuvant BCG was employed with the protein which showed a remarkable 70% inhibition of splenic parasitic multiplication positively correlated with boosted Th1 dominant immune response against lethal L. donovani challenge in hamsters as evidenced by high IFN‐γ and TNF‐α and low IL‐10. In addition, immunological analysis of antibody subclass presented IgG2‐based humoral response besides considerable delayed‐type hypersensitivity and lymphocyte proliferative responses in rLdT‐E/BCG‐treated animals. Our observations indicate the potential of the chimera towards its candidature for an effective vaccine against Leishmania donovani infection.

We recently identified disorganized muscle protein-1 of Brugia malayi (DIM-1bm) as a vaccine candidate for human lymphatic filariasis. The present study wa