Abstract
The Plasmodium vivax Cell-traversal protein for ookinetes and sporozoites (PvCelTOS) plays an important role in the traversal of host cells. Although essential to PvCelTOS progress as a vaccine candidate, its genetic diversity remains uncharted. Therefore, we investigated the PvCelTOS genetic polymorphism in 119 field isolates from five different regions of Brazilian Amazon (Manaus, Novo Repartimento, Porto Velho, Plácido de Castro and Oiapoque). Moreover, we also evaluated the potential impact of non-synonymous mutations found in the predicted structure and epitopes of PvCelTOS. The field isolates showed high similarity (99.3% of bp) with the reference Sal-1 strain, presenting only four Single-Nucleotide Polymorphisms (SNP) at positions 24A, 28A, 109A and 352C. The frequency of synonymous C109A (82%) was higher than all others (p<0.0001). However, the non-synonymous G28A and G352C were observed in 9.2% and 11.7% isolates. The great majority of the isolates (79.8%) revealed complete amino acid sequence homology with Sal-1, 10.9% presented complete homology with Brazil I and two undescribed PvCelTOS sequences were observed in 9.2% field isolates. Concerning the prediction analysis, the N-terminal substitution (Gly10Ser) was predicted to be within a B-cell epitope (PvCelTOS Accession Nos. AB194053.1) and exposed at the protein surface, while the Val118Leu substitution was not a predicted epitope. Therefore, our data suggest that although G28A SNP might interfere in potential B-cell epitopes at PvCelTOS N-terminal region the gene sequence is highly conserved among the isolates from different geographic regions, which is an important feature to be taken into account when evaluating its potential as a vaccine candidate.
Highlights
Malaria is an infectious parasitic disease with high prevalence and morbidity
Our findings indicate that PvCelTOS is an extremely conserved protein, presenting only four Single-Nucleotide Polymorphisms (SNP) in the entire sequences of field isolates from Brazilian Amazon
The two non-synonymous mutations found in our field isolates presented no significant effect on the protein structure and a very low impact on potential T and B-cell epitopes indicated by our epitope prediction
Summary
Malaria is an infectious parasitic disease with high prevalence and morbidity. It is estimated that 3.2 billion people in 95 countries and territories are at risk of being infected and develop the disease. In 2015, malaria caused an estimate of 438,000 deaths, mostly in African children [1]. Among the protozoa species causative of human malaria, Plasmodium vivax, less prevalent than P. falciparum in absolute numbers, presents the world’s largest spread, an increasing morbidity [2] and became the main cause of malaria outside Africa. In Brazil, there are three species of Plasmodium that cause malaria (P. falciparum, P. vivax and P. malariae), approximately 87% of the 142,000 cases reported in 2015 were caused by P. vivax [3]. It is extremely important to develop new methods and intervention strategies to block or reduce this transmission
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