Immunogenicity of PvCyRPA, PvCelTOS and Pvs25 chimeric recombinant protein of Plasmodium vivax in murine model.

In the Americas, P. vivax is the predominant causative species of malaria, a debilitating and economically significant disease. Due to the complexity of the malaria parasite life cycle, a vaccine formulation with multiple antigens expressed in various parasite stages may represent an effective approach. Based on this, we previously designed and constructed a chimeric recombinant protein, PvRMC-1, composed by PvCyRPA, PvCelTOS, and Pvs25 epitopes. This chimeric protein was strongly recognized by naturally acquired antibodies from exposed population in the Brazilian Amazon. However, there was no investigation about the induced immune response of PvRMC-1. Therefore, in this work, we evaluated the immunogenicity of this chimeric antigen formulated in three distinct adjuvants: Stimune, AddaVax or Aluminum hydroxide (Al(OH)3) in BALB/c mice. Our results suggested that the chimeric protein PvRMC-1 were capable to generate humoral and cellular responses across all three formulations. Antibodies recognized full-length PvRMC-1 and linear B-cell epitopes from PvCyRPA, PvCelTOS, and Pvs25 individually. Moreover, mice's splenocytes were activated, producing IFN-γ in response to PvCelTOS and PvCyRPA peptide epitopes, affirming T-cell epitopes in the antigen. While aluminum hydroxide showed notable cellular response, Stimune and Addavax induced a more comprehensive immune response, encompassing both cellular and humoral components. Thus, our findings indicate that PvRMC-1 would be a promising multistage vaccine candidate that could advance to further preclinical studies.

DHA-rich fish oil plays a protective role against experimental cerebral malaria by controlling inflammatory and mechanical events from infection.

Every year, thousands of children, particularly those under 5 years old, die because of cerebral malaria (CM). Following conventional treatment, approximately 25% of surviving individuals have lifelong severe neurocognitive sequelae. Therefore, improved conventional therapies or effective alternative therapies that prevent the severe infection are crucial. Omega-3 (Ω-3) polyunsaturated fatty acids (PUFAs) are known to have antioxidative and anti-inflammatory effects and protect against diverse neurological disorders, including Alzheimer's and Parkinson's diseases. However, little is known regarding the effects of Ω-3 PUFAs against parasitic infections. In this study, C57BL/6 mice received supplemental treatment of a fish oil rich in the Ω-3 PUFA, docosahexaenoic acid (DHA), which was started 15 days prior to infection with Plasmodium berghei ANKA and was maintained until the end of the study. Animals treated with the highest doses of DHA, 3.0 and 6.0 g/kg body weight, had 60 and 80% chance of survival, respectively, while all nontreated mice died by the 7th day postinfection due to CM. Furthermore, the parasite load during the critical period for CM development (5th to 11th day postinfection) was controlled in treated mice. However, after this period all animals developed high levels of parasitemia until the 20th day of infection. DHA treatment also effectively reduced blood-brain barrier (BBB) damage and brain edema and completely prevented brain hemorrhage and vascular occlusion. A strong anti-inflammatory profile was observed in the brains of DHA-treated mice, as well as, an increased number of neutrophil and reduced number of CD8+ T leukocytes in the spleen. Thus, this is the first study to demonstrate that the prophylactic use of DHA-rich fish oil exerts protective effects against experimental CM, reducing the mechanical and immunological events caused by the P. berghei ANKA infection.