Plasmodium vivax AMA1: Implications of distinct haplotypes for immune response

Abstract

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.

Genetic Diversity of Plasmodium vivax Reticulocyte Binding Protein 2b in Global Parasite Populations

“…Population structure analysis further reinforced such a nding on population relatedness. The population differentiation pattern identi ed here was in agreement with other population studies using individual genes [51], microsatellites [54,66], or whole genome sequences [23,24,67]. The distinct parasite genetic structure in PNG may re ect the limited gene ow between PNG and the rest of the world, while the unique RBC polymorphisms in the human populations may have also contributed to this difference [53,66,68,69].…”

Antibodies Against the Plasmodium vivax Apical Membrane Antigen 1 From the Belem Strain Share Common Epitopes Among Other Worldwide Variants

“…Thus, we decided to initiate this study by determining the aa diversity in the ectodomain sequences of PvAMA-1 protein variants. In this approach, we also included the sequences of two recently described Brazilian isolates of P. vivax (PV11-101 (H5) and PV11-90 (H16)) ( Bittencourt et al., 2020 ). A low level of PvAMA-1 polymorphism was found among the global isolates, ranging from 95.2% (Chesson I versus Indonesia XIX) to 99.6% (Belem versus TC103) ( Figure 1A ).…”

“…These findings support the notion that select AMA-1 alleles must be included in vaccine formulation protection against this parasitic disease. Considering that PvAMA-1 sequences display limited polymorphisms ( Gunasekera et al., 2007 ; Arnott et al., 2013 ; Bittencourt et al., 2020 ), the possibility emerges that few recombinant proteins may represent the key alleles needed in a vaccine to cover the entire population of P. vivax .…”

“…A recent study identified polymorphisms predominantly in regions of B cell epitopes of PvAMA-1, using only Brazilian isolates ( Bittencourt et al., 2020 ). Thus, we decided to investigate this scenario by predicting the location of conformational B-cell epitopes in tridimensional structures of Belem as well as in foreign variants with similar and distinct humoral responses (Sal-I and PNG_68_MAS, respectively).…”

“…A recent Brazilian study evaluated the diversity of PvAMA-1 in various isolates and identified 19 haplotypes. Among these sequences, 33 nonsynonymous PvAMA1 amino acid (aa) sites were identified, and 20 of them were determined to be located in predicted B-cell epitopes ( Bittencourt et al., 2020 ). The presence of gene polymorphisms in the sequence of a specific target antigen may compromise its usage as a vaccine candidate.…”