RESUMEN
BACKGROUND: Plasmodium vivax, the major cause of malaria in Latin America, has a large subtelomeric multigene family called vir. In the P. vivax genome, about 20% of its sequences are vir genes. Vir antigens are grouped in subfamilies according to their sequence similarities and have been shown to have distinct roles and subcellular locations. However, little is known about vir subfamilies, especially when comes to their functions. OBJECTIVE: To evaluate the diversity, antigenicity, and adhesiveness of Plasmodium vivax VIR-E. METHODS: Vir-E genes were amplified from six P. vivax isolates from Manaus, North of Brazil. The presence of naturally acquired antibodies to recombinant PvBrVIR-E and PvAMA-1 was evaluated by ELISA. Binding capacity of recombinant PvBrVIR-E was assessed by adhesion assay to CHO-ICAM1 cells. FINDINGS: Despite vir-E sequence diversity, among those identified sequences, a representative one was chosen to be expressed as recombinant protein. The presence of IgM or IgG antibodies to PvBrVIR-E was detected in 23.75% of the study population while the presence of IgG antibodies to PvAMA-1 antigen was 66.25% in the same population. PvBrVIR-E was adhesive to CHO-ICAM1. MAIN CONCLUSIONS: PvBrVIR-E was antigenic and adhesive to CHO-ICAM1.
Asunto(s)
Malaria Vivax , Plasmodium vivax , Adhesividad , Anticuerpos Antiprotozoarios , Antígenos de Protozoos/genética , Brasil , Humanos , Plasmodium vivax/genética , Proteínas Protozoarias/genéticaRESUMEN
In Brazil, Plasmodium vivax infection accounts for around 80% of malaria cases. This infection has a substantial impact on the productivity of the local population as the course of the disease is usually prolonged and the development of acquired immunity in endemic areas takes several years. The recent emergence of drug-resistant strains has intensified research on alternative control methods such as vaccines. There is currently no effective available vaccine against malaria; however, numerous candidates have been studied in the past several years. One of the leading candidates is apical membrane antigen 1 (AMA1). This protein is involved in the invasion of Apicomplexa parasites into host cells, participating in the formation of a moving junction. Understanding how the genetic diversity of an antigen influences the immune response is highly important for vaccine development. In this study, we analyzed the diversity of AMA1 from Brazilian P. vivax isolates and 19 haplotypes of P. vivax were found. Among those sequences, 33 nonsynonymous PvAMA1 amino acid sites were identified, whereas 20 of these sites were determined to be located in predicted B-cell epitopes. Nonsynonymous mutations were evaluated for their influence on the immune recognition of these antigens. Two distinct haplotypes, 5 and 16, were expressed and evaluated for reactivity in individuals from northern Brazil. Both PvAMA1 variants were reactive. Moreover, the IgG antibody response to these two PvAMA1 variants was analyzed in an exposed but noninfected population from a P. vivax endemic area. Interestingly, over 40% of this population had antibodies recognizing both variants. These results have implications for the design of a vaccine based on a polymorphic antigen.
Asunto(s)
Antígenos de Protozoos/genética , Malaria Vivax/inmunología , Malaria Vivax/parasitología , Proteínas de la Membrana/genética , Plasmodium vivax/genética , Proteínas Protozoarias/genética , Dicroismo Circular , ADN Protozoario/genética , Epítopos de Linfocito B , Haplotipos , Humanos , Malaria Vivax/epidemiología , Mutación , Plasmodium vivax/inmunología , Conformación Proteica , Proteínas RecombinantesRESUMEN
BACKGROUND Plasmodium vivax, the major cause of malaria in Latin America, has a large subtelomeric multigene family called vir. In the P. vivax genome, about 20% of its sequences are vir genes. Vir antigens are grouped in subfamilies according to their sequence similarities and have been shown to have distinct roles and subcellular locations. However, little is known about vir subfamilies, especially when comes to their functions. OBJECTIVE To evaluate the diversity, antigenicity, and adhesiveness of Plasmodium vivax VIR-E. METHODS Vir-E genes were amplified from six P. vivax isolates from Manaus, North of Brazil. The presence of naturally acquired antibodies to recombinant PvBrVIR-E and PvAMA-1 was evaluated by ELISA. Binding capacity of recombinant PvBrVIR-E was assessed by adhesion assay to CHO-ICAM1 cells. FINDINGS Despite vir-E sequence diversity, among those identified sequences, a representative one was chosen to be expressed as recombinant protein. The presence of IgM or IgG antibodies to PvBrVIR-E was detected in 23.75% of the study population while the presence of IgG antibodies to PvAMA-1 antigen was 66.25% in the same population. PvBrVIR-E was adhesive to CHO-ICAM1. MAIN CONCLUSIONS PvBrVIR-E was antigenic and adhesive to CHO-ICAM1.