Introduction
Leishmaniasis is a parasitic disease transmitted by the bites of infected sand flies. It is one of the most neglected disease of tropical countries, Leishmaniasis also known as “Kala Azhar”, is caused by a single-celled protozoan parasite. A parasite, Leishmania that enters the human body when infected sand flies introduce it into the skin during their blood meals. This malaise presents a range of clinical variations having diseases of varied etiologies that are caused by approximately 20 different Leishmania parasite species, from localized skin lesions that typically heal quickly to mucosal and visceral forms of leishmaniasis that can be life-threatening when left untreated. On a global scale, approximately 350 million individuals, primarily those in less affluent circumstances, face the risk of contracting this potentially fatal disease. India is one of three countries that account for an estimated 300,000 cases of visceral leishmaniasis occurring annually.
Leishmaniasis is a disease that is most likely to be controlled by a successful vaccination program. The relatively complicated leishmanial life cycle and the fact that recovery from a primary infection renders the host resistant to subsequent infections indicate that a vaccine is feasible. Evidence from studies in animal models, mainly mice, indicates that protection can be achieved upon immunization with various vaccine formulations; however, traditional vaccine method of injecting a weakened form of a virus or bacteria into the body have been disappointing when tested in the field. Besides the lackluster economic outlook for a leishmaniasis vaccine, there has been an efficacious solution found to it and it is called DNA vaccines. DNA vaccination is a technique for protecting a host against disease by injecting a genetically engineered DNA so cells directly produce an antigen, resulting in a protective immunological response.
How DNA vaccines work against Leishmaniasis?
Recently, some investigators advocated the protective efficacy of DNA vaccines, which induces the T cell-based immunity against visceral Leishmania's. The vaccine antigens are selected as conserved in various Leishmania species and provide a viable strategy for DNA vaccine development. DNA vaccine development against VL as of now is not enough and technological advancement is required. Improved formulations and methods of delivery are being added, which increase the uptake of DNA vaccine by cells; optimization of vaccine vectors/encoded antigens to augment and direct the host immune response in VL. Studies in mice show that protective immunity to Leishmania infection requires the development of interleukin-12-dependent, parasite-specific Th1 responses, characterized by interferon-γ and tumor necrosis factor production by CD4+ T cells. These inflammatory cytokines are required for the generation of reactive oxygen and nitrogen species by infected macrophages that enables killing of intracellular parasites. Recent advances have also been made in understanding immunoregulatory mechanisms that suppress parasite-specific CD4+ T-cell responses in human VL patients. These include the discovery that interleukin-10 produced by CD4+ T cells is a potent, autocrine inhibitor of interferon-γ production and promotes parasite persistence in spleen tissue from VL patients. Thus, interleukin-10 has been identified as a potential therapeutic target for use in combination with drug therapy or to improve therapeutic vaccine efficacy. The generation of immunological memory is a requirement of effective vaccination. Studies on the generation of effector and central memory CD4+ T cells indicate that central memory T cells mediate long-term immunity to L. major infection, even in the absence of persistent parasites. Combined with our understanding about the types of immune responses required for killing parasites and those that suppress this immunity, means that developing vaccines against leishmaniasis is a realistic goal.
The effect of HbR-DNA vaccination. (a) Mice and hamsters were vaccinated with the HbR-DNA vaccine before infection with L. donovani promastigotes (1). The antigens were presented by antigen-presenting cells (APC) to CD4+ and CD8+ T cells in context of MHC-II and MHC-I molecules, respectively (2). This led to the enhanced proliferation of both CD4+ and CD8+ T cells (3) and generation of multifunctional CD4+ and CD8+ T cells. CD4+ T cells enhanced antibody generation by B cells/plasma cells (4). The combined effect of increased multifunctional CD4+ and CD8+ T cells and antibody resulted in complete clearance of the parasite (5). (b) Non-vaccinated mice and hamsters were infected with L. donovani promastigotes (1). Antigens were presented by APC to CD4+ and CD8+ T cells, (2) which resulted in limited T-cell proliferation and the generation of interleukin-10 producing cells (3) leading to enhanced parasite growth (4)
Conclusion
A new ray of hope has emerged in the battle against Leishmaniasis, a neglected tropical disease transmitted by infected sand flies. DNA vaccines are at the forefront of this optimism, as they work to stimulate T cell-based immunity against the disease. With breakthroughs in vaccine formulation, improved delivery methods, and a deeper understanding of immune responses, there is newfound optimism that we can effectively combat this debilitating ailment in the near future.
References
by - SANIKA KHARAT
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