An innovative inmunotherapeutic approach for controlling american tegumentary leishmaniasis

ARRIETA, VICTORIA J.; GERMANÓ MARÍA JOSÉ; BRUNA FLAVIA ALEJANDRA; SÁNCHEZ MARÍA VICTORIA; LOZANO ESTEBAN SEBASTIÁN; CARGNELUTTI DIEGO ESTEBAN

San Luis

Congreso; LXXI Reunión Anual de la Sociedad Argentina de Inmunología; 2023

Sociedad Argentina de Inmunología

Leishmaniasis, an expanding parasitic zoonosis in South America, has been designated as one of the neglected diseases by the World Health Organization due to its disproportionate impact on low-income populations with limited access to healthcare. Within Argentina, leishmaniasis endemically affects regions encompassing 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 notable for its ability to induce a wide spectrum of clinical manifestations, ranging from localized cutaneous leishmaniasis to severe forms characterized by mutilation, incapacitation, and often a poor response to treatment. Currently, no vaccine is available for the prevention of leishmaniasis in humans, and the existing treatments, such as Glucantime, are unsatisfactory due to their high toxicity, cost, complex administration and the emergence of resistant strains. Hence, there is a pressing need to explore innovative immunotherapeutic alternatives, especially based on first-generation vaccines. In our research, we assessed the effectiveness of a prophylactic vaccine composed of total antigens from L. amazonensis (LTA) combined with a Toll-like receptor-3 (TLR-3) agonist, [Poly (I:C)]. Previous studies have indicated that this prophylactic vaccine formulation can induce a protective Th1-type immune response, characterized by elevated 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 1x104 L. amazonensis promastigotes and treated with the LTA+Poly (I:C) formulation, administered in up to 5 subcutaneous doses at 7-day intervals. We employed PBS, Glucantime, LTA, and Poly (I:C) as control groups. Parameters such as the swelling at the infection site, weight of lesion, parasite load and humoral immune response were thoroughly analyzed. The evaluation of the statistical significance of the data was carried out with parametric or non-parametric tests. Our findings revealed that Poly (I:C) managed to control the infection, resulting in reduced swelling, lower parasite load, and decreased IgG levels compared to the LTA+Poly (I:C) group, which exhibited contrasting outcomes. This study highlights how the formulation of LTA+Poly (I:C) at a specific concentration may elicit an inadequate immune response. As part of our future perspective, based on these results, we intend to focus on further optimizing the therapeutic dose of Poly (I:C) to conduct in-depth investigations into its response against leishmaniasis.