Triagem de novas formulações vacinais e imunoterápicas para interromper a transmissão da leishmaniose visceral canina.

Abstract

Canine Visceral Leishmaniasis (CVL) is a disease caused by the protozoan Leishmania infantum, transmitted mainly by sand flies, with Lutzomyia longipalpis being the main insect vector in Brazil. The disease is endemic in more than 70 countries, including southeastern Europe, Asia, and Central and South America. To date, there is no effective vaccine to control CVL or treatment that results in a definitive parasitological cure. Since cases of CVL usually precede those of human visceral leishmaniasis, it is crucial to find an effective therapy. Therefore, our research group is focused on the development of new vaccines. One of them involves the recombinant protein of L. infantum, L22.4_CHP, combined with antigens from the insect vector Lutzomyia longipalpis. The objective of this study was to develop an immunobiological to act as a vaccine or immunotherapy against CVL, and that also influences in the insect vector. This would result in greater success in blocking transmission of the parasite to other sand flies, reducing the risk of transmission to healthy dogs and humans. The main results indicated that in both the vaccine and immunotherapy approaches, the formulation containing the L22.4_CHP antigen in association with sandfly antigens was immunogenic, with the production of high levels of IgG against the vaccine antigens. In addition, there was production of IgG1 and IgG2a in mice, indicating that the L22.4_CHP antigen is capable of inducing a mixed immune response profile of types 1 and 2. When considering together the results of the vaccine and immunotherapy trials, we can conclude that the recombinant protein L22.4_CHP in association with sandfly antigens proved to be safe, in addition to inducing protection/reduction of the parasite load in mice and dogs. In combination with phage B5, this approach showed encouraging results, indicating potential to inhibit parasite binding to phlebotomine cells. However, it is still necessary to improve therapeutic protocols and perform further tests to evaluate the blocking of transmission in the insect vector. New studies, including a larger number of dogs, may validate the use of the antigens evaluated in this study as a vaccine and immunotherapeutic agent capable of not only reducing the parasite load in target organs of the protozoan, but also interfering in the dynamics of parasite transmission in phlebotomines.