Camila Freitas, Federal University of Minas Gerais, Brazil - VALIDATE Fellow
Preclinical evaluation of a novel recombinant chimeric vaccine for protection against tegumentary leishmaniasis
Project Aims
Tegumentary leishmaniasis (TL) is a neglected tropical disease complex that affects millions of people worldwide, particularly in low- and middle-income countries (LMICs). It is caused by various Leishmania species, leading to a wide spectrum of clinical manifestations ranging from self-limiting skin lesions to severe, disfiguring, and mutilating lesions that cause patient morbidity. Treatment for TL is toxic, expensive, and/or requires prolonged administration; making the disease management challenging and increasing the risk of relapses and reinfection. Despite the urgent need for better control measures, no human vaccine is available for TL. However, vaccination represents a promising, cost-effective, and innovative strategy to protect healthy people against infection. In this context, we propose to develop and test a novel recombinant chimeric vaccine composed of distinct T-cell epitopes from immunogenic proteins which are conserved in Leishmania braziliensis, Leishmania amazonensis, and Leishmania major species, the species responsible for most of the TL cases worldwide. The T-cell epitopes combined with a protein-encoding gene will be cloned, expressed, purified and tested in a murine model associated with immune adjuvants, in order to evaluate the protective efficacy against infection caused by L. major and L. amazonensis. Several parasitological and immunological techniques will be applied to evaluate the vaccine efficacy. In addition, the chimeric protein will be used in in vitro experiments to stimulate human peripheral blood mononuclear cells (PBMCs) from healthy donors, allowing the assessment of cellular proliferation and cytokine production in cell cultures. The experiments aim to determine whether the chimeric protein combined with an adjuvant can protect against Leishmania infection a mammalian model, as well as to determine if it will be immunogenic in humans. The results will provide essential preclinical data to support future studies evaluating the protective efficacy against the disease in humans.
Find out more about Dr Camila Freitas here.
