Avaliação da resposta imune por via de mucosa contra antígenos candidatos a vacina para malária causada por Plasmodium falciparum

Abstract

Malaria is the most important parasitic disease in the world, with Plasmodium falciparum responsible for the majority of deaths. The latest data released by the World Health Organization estimates that there were 241 million cases of malaria registered in 2020, with around 627 thousand deaths. In the face of this alarming reality, there is a need to develop effective and economically accessible vaccine strategies against malaria. The objective of this study was to evaluate the immune response profile induced by intranasal administration of recombinant rPfMSP-3 and rPfCSP proteins from P. falciparum in a murine model. The rPfMSP-3 and rPfCSP proteins were expressed in a bacterial host, subsequently purified using the Immobilized Metal Affinity Chromatography (IMAC) technique and quantified using the Bradford method. To evaluate the immunological response, female BALB/c mice, aged between 6 and 8 weeks, were divided into 10 groups containing 7 animals each. These animals were immunized intranasally with different concentrations of recombinant proteins, receiving two doses of the immunizer (rPfCSP, rPfMSP-3, and PBS 1x) with an interval of 14 days. Blood samples were collected before the first immunization and on days 14 and 28 to evaluate the induced immune response. The production of anti-rPfMSP-3 and anti-rPfCSP antibodies was analyzed using indirect enzyme immunoassay and merozoite invasion test, while the serum cytokine profile was evaluated using flow cytometry. The results of this study revealed that the recombinant proteins used have an immunogenic profile, with emphasis on rPfCSP, which demonstrated greater immunogenicity in the study. rPfMSP-3 also induced a significant humoral response, and anti-rPfMSP-3 antibodies were able to inhibit merozoite invasion into red blood cells. These data are promising and could serve as a basis for the development of new malaria vaccine strategies, particularly those that explore mucosal administration in murine models, without the need for adjuvants.