Plasmodium vivax circumsporozoite protein: genetic and immunological aspects

It is well established that infection by Plasmodium vivax is a result of host-parasite interactions. This study evaluated polymorphisms in the IL1 and IL2 genes and of the central portion of the circumsporozoite protein (CSP)and correlated them with the cytokine profiles, anti-CSP antibody levels and parasitic loads of 138 individuals naturally infected with P. vivax in an endemic area of the Brazilian Amazon. Molecular diagnosis of P. vivax and variants was performed using the PCR-RFLP method, and IL-1β and IL-2 cytokine levels were detected by flow cytometry. IL1B -511C>T, IL2 -330T>G and IL2 +114T>G polymorphisms were identified using PCR-RFLP and allele-specific PCR. CSP antibodies were measured by ELISA. Three variants of P. vivax CSP were identified, and VK247 was found to be the most frequent. However, the prevalence and magnitude of IgG antibodies were higher for the VK210 variant. Furthermore, the antibody response to the CSP variants was not associated with the presence of the variant in the infection. Significant differences were observed between SNP -511T>C in the IL1B gene and levels of antibodies to the VK247 and P. vivax-like variants, but there were no associations between SNPs in genes IL1 and IL2 and their plasma products. Studies of associations of cytokine gene SNPs in the humoral immune response to malaria are still incomplete, and the results have been contradictory. Given that the evolution of malaria results from the interaction of factors inherent to both parasite and host, this study helped to identify genetic variants that may influence the humoral immune response against malaria, particularly P. vivax.