Vaccine Development Against Leishmania donovani

Abstract

Visceral leishmaniasis (VL) caused by Leishmania donovani and Leishmania infantum/chagasi represents the second most challenging infectious disease worldwide, leading to nearly 500,000 new cases and 60,000 deaths annually. Zoonotic VL caused by L. infantum is a re-emergent canid zoonoses which represents a complex epidemiological cycle in the New world where domestic dogs serve as a reservoir host responsible for potentially fatal human infection and where dog culling is the only measure for reservoir control. Life-long immunity to VL has motivated development of prophylactic vaccines against the disease but very few have progressed beyond the experimental stage. No licensed vaccine is available till date against any form of leishmaniasis. High toxicity and increasing resistance to the current chemotherapeutic regimens have further complicated the situation in VL endemic regions of the world. Advances in vaccinology, including recombinant proteins, novel antigen-delivery systems/adjuvants, heterologous prime-boost regimens and strategies for intracellular antigen presentation, have contributed to recent advances in vaccine development against VL. Attempts to develop an effective vaccine for use in domestic dogs in areas of canine VL should be pursued for preventing human infection. Studies in animal models and human patients have revealed the pathogenic mechanisms of disease progression and features of protective immunity. This review will summarize the accumulated knowledge of pathogenesis, immune response, and prerequisites for protective immunity against human VL. Authors will discuss promising vaccine candidates, their developmental status and future prospects in a quest for rational vaccine development against the disease. In addition, several challenges such as safety issues, renewed and coordinated commitment to basic research, preclinical studies and trial design will be addressed to overcome the problems faced in developing prophylactic strategies for protection against this lethal infection.

Immunogenicity and efficacy of recombinant 78 kDa antigen of Leishmania donovani formulated in various adjuvants against murine visceral leishmaniasis

“…For the past 20 years, DNA cloning and characterization of genes encoding parasite proteins suitable for the development of defined vaccines have been carried out [7] . Several native and recombinant antigens, tested in murine models, have shown different degrees of protection [1,[8][9][10][11] . Recombinant Ldccys1 protein elicits protective immune responses in Leishmania chagasi infected BALB/c mice [12] .…”

Genetically Modified Live Attenuated Leishmania donovani Parasites Induce Innate Immunity through Classical Activation of Macrophages That Direct the Th1 Response in Mice

“…he protozoan parasite Leishmania donovani is one of the major causative agents of visceral leishmaniasis (VL), which is the second most challenging infectious disease worldwide, with nearly 500,000 new cases and 60,000 deaths annually (1).…”

Drug Delivery: Lessons to Be Learnt From Leishmania Studies

“…Determination of host immune responses showed that resiquimod liposome treatment was associated with enhanced IFN-γ and IL-10 production by splenocytes activated with specific antigen compared with control or carrier-alone groups. These two cytokines act antagonistically as IFN-γ production stimulates macrophages to kill Leishmania and is associated with protection against L. donovani infection whereas IL-10 suppresses macrophage activation and its production is associated with susceptibility [52]. However, the relative local concentration of each cytokine at the site of infection will be important in determining whether the immunostimulatory effects aid parasite clearance or not.…”