Plasmodium falciparum Variability and Immune Evasion Proceed from Antigenicity of Consensus Sequences from DBL6ε; Generalization to All DBL from VAR2CSA

Philippe Deloron,Cyril Badaut,Jacqueline Milet,Luzia Helena Carvalho

doi:10.1371/journal.pone.0054882

Abstract

We studied all consensus sequences within the four least ‘variable blocks’ (VB) present in the DBL6ε domain of VAR2CSA, the protein involved in the adhesion of infected red blood cells by Plasmodium falciparum that causes the Pregnancy-Associated Malaria (PAM). Characterising consensus sequences with respect to recognition of antibodies and percentage of responders among pregnant women living in areas where P. falciparum is endemic allows the identification of the most antigenic sequences within each VB. When combining these consensus sequences among four serotypes from VB1 or VB5, the most often recognized ones are expected to induce pan-reactive antibodies recognizing VAR2CSA from all plasmodial strains. These sequences are of main interest in the design of an immunogenic molecule. Using a similar approach than for DBL6ε, we studied the five other DBL and the CIDRpam from VAR2CSA, and again identified VB segments with highly conserved consensus sequences. In addition, we identified consensus sequences in other var genes expressed by non-PAM parasites. This finding paves the way for vaccine design against other pathologies caused by P. falciparum.

Highlights

In endemic areas, pregnancy-associated Plasmodium falciparum malaria (PAM) causes maternal anaemia, stillbirth and delivery of low birth weight (LBW) babies, the single most important determinant of mortality during the first year of life of African infants
We compared the number of variable blocks (VB) peptide sequences recognized by protein G purified IgG from the plasma of women infected by P. falciparum (n = 39, mean age = 24) or not infected (n = 41, mean age = 25) during their pregnancy (Figure 1A)
Since consensus sequences from VB are present in parasites from all endemic areas [14,19], our results suggest that a vaccine constituted by these peptides from these four VB could induce antibodies against essentially all P. falciparum isolates involved in pregnancy-associated malaria

Summary

Introduction

Pregnancy-associated Plasmodium falciparum malaria (PAM) causes maternal anaemia, stillbirth and delivery of low birth weight (LBW) babies, the single most important determinant of mortality during the first year of life of African infants. WHO considers malaria in pregnancy as "one of the most important preventable causes of low birth weight deliveries worldwide" and "a major cause of severe maternal anaemia contributing to maternal mortality" [1]. I.e. the massive infection of the placenta by cytoadhering P. falciparum parasites, is a major contributor to PAM. It is more pronounced in primigravidae, where it is associated with a two-fold increased risk to give birth to a LBW baby [2]. Infants born to women with PAM are more susceptible to P. falciparum infection in the first year of life [4,5] and is a major contributor to infant morbidity and mortality

Methods

Results

Conclusion