Avaliação da eficácia vacinal e imunogenicidade de antígenos de Ascaris suum na ascaridíase experimental

Abstract

Human ascariasis has a cosmopolitan distribution and is also characterized as the most prevalent and neglected tropical disease in the world. Recent studies estimate that about 800 million people are infected worldwide. Strategies for prophylactic interventions against human ascariasis are limited, since the education system in health and basic sanitation in regions endemic for the disease is extremely precarious, resulting in high reinfection rates even after specific treatment. In order to improve the quality of life and lower morbidity, especially in individuals from endemic areas, we are lookinf for the development of a vaccine that would guarantee the long-term protection against the main soil transmitted helminths in general. Thus, through immunization with different Ascaris suum antigens, being: crude extract of adult worm; crude extract of adult worm tegument; and crude extract of infective larvae, the present study aimed at the identification of new vaccine candidates aiming the development of a new prophylactic strategy against ascariasis. In this study we evaluated the vaccine efficacy by quantifying the parasite load in the lung and alveolar bronchoalveolar lavage of animals previously immunized and then challenged with infecting eggs of the parasite. In addition, the immunogenicity of the vaccine candidates was evaluated through the systemic and tissue cytokine profile, as well as the pulmonary function and the leukocyte profile present in the bronchoalveolar lavage. Finally, the humoral participation in the protection of parasite load and the profile of antibody production after immunizations and after infection were also evaluated. Our results demonstrated a significant reduction of parasite load in the animals immunized with A. suum antigens with the crude larval antigen reaching approximately 61% protection, followed by the crude tegument antigen with 59% and finally the crude adult worm antigen with 51% load reduction. Regarding the systemic cytokine profile, a significant regulation of the IL-5 cytokine in the animals immunized with the different A. suum antigens and a significant IL-10 production induced by the TEG antigen in relation to the non-immunized animals was observed. As for antigen-specific IgG antibody levels, a gradual and progressive increase was observed according to the immunizations with an increase mainly of IgG1 and IgG3 subclasses. Subsequently, in view of the investigation of the humoral participation in the reduction of the load, we observed that animals submitted to the passive transfer protocol with anti-antigen antibodies of A. suum presented approximately 65% protection against infection. From these results, we can infer that A. suum antigens are potential candidates for research and prove that it is feasible to use and develop a vaccine, mainly aimed at controlling and reducing the parasite burden in infected individuals in endemic regions.