Plasmodium vivax contains approximately 5400 coding genes, more than 40% of which code for hypothetical proteins that have not been functionally characterized. In a previous preliminary screening using pooled serum samples, numerous hypothetical proteins were selected from among those that were highly transcribed in the schizont-stage of parasites, and highly antigenic P. vivax candidates including hypothetical proteins were identified. However, their immunological and functional activities in P. vivax remain unclear. From these candidates, we investigated a P. vivax 50-kDa protein (Pv50, PVX_087140) containing a highly conserved signal peptide that shows high transcription levels in blood-stage parasites.

There is an urgent need for an effective vaccine to control and eradicate malaria, one of the most serious global infectious diseases. Plasmodium merozoite surface protein 4 (MSP4) has been listed as a blood-stage subunit vaccine candidate for malaria. Infection with Plasmodium ovale species including P. ovale wallikeri and P. ovale curtisi, is also a source of malaria burden in tropical regions where it is sometimes mixed with other Plasmodium species. However, little is known about P. ovale MSP4.

Plasmodium ovale is widely distributed across tropical regions and has two closely related but distinct species, namely P. ovale curtisi and P. ovale wallikeri. Combining genetic characterization with the immunogenicity of merozoite surface protein-8 (MSP-8) supports considering MSP-8 as a candidate target for blood-stage vaccines against malaria. However, no previous studies have focused on characterizing the genetic diversity and immunogenicity of PoMSP-8.

The development of an effective malarial vaccine is an urgent need. Most glycosylphosphatidylinositol (GPI)-anchored proteins of Plasmodium parasites are exposed to neutralizing antibodies, and several are advanced vaccine candidates. In the present study, Plasmodium vivax Pv32 (PVX_084815) as a hypothetical, predicted GPI-anchored and cysteine-rich motif was identified from our previous findings with a focus on its antigenic profiling. The orthologue gene pv32, a predicted GPI anchor of P. falciparum PF3D7_1434400, has still not been well studied.

The Plasmodium vivax merozoite surface protein 1 paralog (PvMSP1P), which has epidermal growth factor (EGF)-like domains, was identified as a novel erythrocyte adhesive molecule. This EGF-like domain (PvMSP1P-19) elicited high level of acquired immune response in patients. Antibodies against PvMSP1P significantly reduced erythrocyte adhesion activity to its unknown receptor. To determine PvMSP1P-19-specific antibody function and B-cell epitopes in vivax patients, five monoclonal antibodies (mAbs) and 18-mer peptides were generated. The mAb functions were determined by erythrocyte-binding inhibition assay and invasion inhibition assay with P. knowlesi. B-cell epitopes of PvMSP1P-19 domains were evaluated by peptide microarray. The pvmsp1p-19 sequences showed limited polymorphism in P. vivax worldwide isolates. The 1BH9-A10 showed erythrocyte binding inhibitory by interaction with the N-terminus of PvMSP1P-19, while this mAb failed to recognize PkMSP1P-19 suggesting the species-specific for P. vivax. Other mAbs showed cross-reactivity with PkMSP1P-19. Among them, the 2AF4-A2 and 2AF4-A6 mAb significantly reduced parasite invasion through C-terminal recognition. The linear B-cell epitope in naturally exposed P. vivax patient was identified at three linear epitopes. In this study, PvMSP1P-19 N-terminal-specific 1BH9-A10 and C-terminal-specific 2AF4 mAbs showed functional activity for epitope recognition suggesting that PvMSP1P may be useful for vaccine development strategy for specific single epitope to prevent P. vivax invasion.

Plasmodium merozoite surface protein-1 (MSP-1) is released into the bloodstream during merozoite invasion, and thus represents a crucial malarial vaccine target. Although substantial research effort has been devoted to uncovering the genetic diversity of MSP-1 for P. falciparum and P. vivax, there is minimal information available regarding the genetic profiles and structure of P. ovale. Therefore, the aim of the present study was to determine the extent of genetic variation among two subspecies of P. ovale by characterizing the MSP-1 N-terminal sequence at the nucleotide and protein levels.

Merozoite surface protein 1 (MSP1) plays an essential role in erythrocyte invasion by malaria parasites. The C-terminal 19-kDa region of MSP1 has long been considered one of the major candidate antigens for a malaria blood-stage vaccine against Plasmodium falciparum. However, there is limited information on the C-terminal 19-kDa region of Plasmodium ovale MSP1 (PoMSP119). This study aims to analyze the genetic diversity and immunogenicity of PoMSP119.

Thirty-one glycosylphosphatidylinositol (GPI)-anchored proteins of Plasmodium vivax, merozoite surface protein 1 (MSP1), MSP1 paralogue, MSP4, MSP5, MSP8, and MSP10 have been reported from homologs of Plasmodium falciparum by gene annotation with bioinformatics tools. These GPI-anchored proteins contain two epidermal growth factor (EGF)-like domains at its C-terminus. Here, P. vivax merozoite surface protein 8 (PvMSP8) are considered as potential targets of protective immunity.

Malaria is a public health concern worldwide, and Togo has proven to be no exception. Effective approaches to provide information on biological insights for disease elimination are therefore a research priority. Local selection on malaria pathogens is due to multiple factors including host immunity. We undertook genome-wide analysis of sequence variation on a sample of 10 Plasmodium falciparum (Pf) clinical isolates from Togo to identify local-specific signals of selection. Paired-end short-read sequences were mapped and aligned onto > 95% of the 3D7 Pf reference genome sequence in high fold coverage. Data on 266 963 single nucleotide polymorphisms were obtained, with average nucleotide diversity π = 1.79 × 10-3. Both principal component and neighbor-joining tree analyses showed that the Togo parasites clustered according to their geographic (Africa) origin. In addition, the average genome-wide diversity of Pf from Togo was much higher than that from other African samples. Tajima's D value of the Togo isolates was -0.56, suggesting evidence of directional selection and/or recent population expansion. Against this background, within-population analyses identifying loci of balancing and recent positive selections evidenced that host immunity has been the major selective agent. Importantly, 87 and 296 parasite antigen genes with Tajima's D values > 1 and in the top 1% haplotype scores, respectively, include a significant representation of membrane proteins at the merozoite stage that invaded red blood cells (RBCs) and parasitized RBCs surface proteins that play roles in immunoevasion, adhesion, or rosetting. This is consistent with expectations that elevated signals of selection due to allele-specific acquired immunity are likely to operate on antigenic targets. Collectively, our data suggest a recent expansion of Pf population in Togo and evidence strong host immune selection on membrane/surface antigens reflected in signals of balancing/positive selection of important gene loci. Findings from this study provide a fundamental basis to engage studies for effective malaria control in Togo.