Abstract
Over the last four decades, significant efforts have been invested to develop vaccines against malaria. Although most efforts are focused on the development of P. falciparum vaccines, the current availability of the parasite genomes, bioinformatics tools, and high throughput systems for both recombinant and synthetic antigen production have helped to accelerate vaccine development against the P. vivax parasite. We have previously in silico identified several P. falciparum and P. vivax proteins containing α-helical coiled-coil motifs that represent novel putative antigens for vaccine development since they are highly immunogenic and have been associated with protection in many in vitro functional assays. Here, we selected five pairs of P. falciparum and P. vivax orthologous peptides to assess their sero-reactivity using plasma samples collected in P. falciparum- endemic African countries. Pf-Pv cross-reactivity was also investigated. The pairs Pf27/Pv27, Pf43/Pv43, and Pf45/Pv45 resulted to be the most promising candidates for a cross-protective vaccine because they showed a high degree of recognition in direct and competition ELISA assays and cross-reactivity with their respective ortholog. The recognition of P. vivax peptides by plasma of P. falciparum infected individuals indicates the existence of a high degree of cross-reactivity between these two Plasmodium species. The design of longer polypeptides combining these epitopes will allow the assessment of their immunogenicity and protective efficacy in animal models.
Highlights
Malaria disease was globally estimated at 228 million of cases in 2018 [1]
Previous work published by Cespedes et al reported the recognition of 50 α-helical coiled coil peptides by human plasma samples from Colombia and Papua New Guinea (PNG), identifying 38 peptides that showed the highest sero-reactivity [28]
In the present study we expanded the analysis of the 38 peptides and their orthologous by testing them with three panels of plasma samples obtained from African donors living in Mali, Tanzania or Burkina Faso (Supplementary Table 1)
Summary
Malaria disease was globally estimated at 228 million of cases in 2018 [1]. Plasmodium falciparum and P. vivax are the two most important parasites in terms of infection prevalence and global distribution, and are responsible for more than 98% of global malaria clinical cases. Resistance to artemisinin, the main current anti-malarial treatment for P. falciparum, has been identified in several countries [3,4,5,6], and a reduction of the sensitivity of P. vivax parasites to antimalarials like chloroquine and primaquine has been reported [7,8,9,10] This represents an enormous challenge to malaria eradication and indicates the need for new control and elimination strategies. The availability of the Plasmodium genome and proteome as well as of bioinformatics tools have allowed the identification of parasite proteins containing specific domains with functional importance such as α-helical coiled-coil motifs. The corresponding domains were synthesized and tested for their reactivity with sera of individuals from malaria-endemic areas [21, 28, 31]
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