RESEARCH AND DEVELOPMENT OF NEW INMUNOTHERAPEUTIC STRATEGIES AGAINST AMERICAN TEGUMENTARY LEISHMANIASIS

ARRIETA VICTORIA JUDITH; GERMANÓ MARÍA JOSÉ; BRUNA FLAVIA ALEJANDRA; SÁNCHEZ MARÍA VICTORIA; LOZANO ESTEBAN SEBASTIÁN; CARGNELUTTI DIEGO ESTEBAN

San Luis

Congreso; XXXIX Reunión Anual de la Sociedad de Biología de Cuyo; 2021

Universidad Nacional de San Luis

Leishmaniasis is an expanding parasitic zoonosis in South America and is considered as one of the neglected diseases by the World Health Organization because it mainly affects the low-income population and with limited access to health services. In Argentina, the endemic area of leishmaniasis corresponds to the provinces of Salta, Jujuy, Tucumán, Catamarca, Santiago del Estero, Chaco, Formosa, Misiones, and Corrientes. Leishmania amazonensis, one of the etiological agents of leishmaniasis in our country, is distinguished by its ability to cause a wide spectrum of clinical manifestations: from localized cutaneous leishmaniasis, to the most serious forms (such as mutilating, incapacitating and frequently with little response to treatment). Currently, there is no vaccine for the prevention of leishmaniasis in humans and current treatments for leishmaniasis (Glucantime) are unsatisfactory due to the associated high toxicity, cost, complex administration, and the emergence of resistant strains. Therefore, we consider it necessary to develop innovative immunotherapeutic alternatives based on first generation vaccines. In this work, we evaluated the effect of a prophylactic vaccine formulated with total antigens of L. amazonensis(LTA) and an agonist of TLR-3 [Poly (I:C)]. It has been reported that such prophylactic vaccine formulation has generated a protective immune response of the Th1 type, characterized by high production of IgG2a and IFN-γ with low levels of IL-4 and IL-10. Female BALB/c mice were infected in the right hind paw pad with 1×104 L. amazonensis promastigotes and treated with LTA+Poly (I:C) formulation, that were administrated up to five subcutaneous doses with a 7-day interval. PBS, Glucantime, LTA and Poly (I:C), were used as control groups. We analyzed different parameters like the swelling of the infection site, parasite load, histopathology, splenic index, and determination of the humoral immune response. We observed that Poly (I:C) managed to control the infection, generate less swelling, maintain the histoarchitecture, present a lower parasite load, and decrease IgG levels compared to LTA+Poly (I:C), which presented opposite results. In this study we show how the formulation of LTA+Poly (I:C) at a certain concentration generates an inadequate immune response while the formulation with Poly (I:C) alone shows a similar response to that of Glucantime, indicating a possible new alternative to treatment of leishmaniasis. As a future perspective, based on these results, we will focus on Poly (I:C) and will seek to adjust the therapeutic dose to further analyze its response to the disease