Abstract
BackgroundPregnant women acquire protective antibodies that cross-react with geographically diverse placental Plasmodium falciparum isolates, suggesting that surface molecules expressed on infected erythrocytes by pregnancy-associated malaria (PAM) parasites have conserved epitopes and, that designing a PAM vaccine may be envisaged. VAR2CSA is the main candidate for a pregnancy malaria vaccine, but vaccine development may be complicated by its sequence polymorphism.MethodsThe dynamics of P. falciparum genotypes during pregnancy in 32 women in relation to VAR2CSA polymorphism and immunity was determined. The polymorphism of the msp2 gene and five microsatellites was analysed in consecutive parasite isolates, and the DBL5ε + Interdomain 5 (Id5) part of the var2csa gene of the corresponding samples was cloned and sequenced to measure variation.ResultsIn primigravidae, the multiplicity of infection in the placenta was associated with occurrence of low birth weight babies. Some parasite genotypes were able to persist over several weeks and, still be present in the placenta at delivery particularly when the host anti-VAR2CSA antibody level was low. Comparison of diversity among genotyping markers confirmed that some PAM parasites may harbour more than one var2csa gene copy in their genome.ConclusionsHost immunity to VAR2CSA influences the parasite dynamics during pregnancy, suggesting that the acquisition of protective immunity requires pre-exposure to a limited number of parasite variants. Presence of highly conserved residues in surface-exposed areas of the VAR2CSA immunodominant DBL5ε domain, suggest its potential in inducing antibodies with broad reactivity.
Highlights
Pregnant women acquire protective antibodies that cross-react with geographically diverse placental Plasmodium falciparum isolates, suggesting that surface molecules expressed on infected erythrocytes by pregnancyassociated malaria (PAM) parasites have conserved epitopes and, that designing a PAM vaccine may be envisaged
Two patterns of P. falciparum dynamics in pregnant women are described in this study according to the antiVAR2CSA IgG level of the women at enrolment
The correlation between low levels of anti-VAR2CSA antibodies and the presence of persisting parasite genotypes in the placenta at delivery suggests that the acquisition of a protective immunity in pregnant women is gradual
Summary
Pregnant women acquire protective antibodies that cross-react with geographically diverse placental Plasmodium falciparum isolates, suggesting that surface molecules expressed on infected erythrocytes by pregnancyassociated malaria (PAM) parasites have conserved epitopes and, that designing a PAM vaccine may be envisaged. Plasmodium falciparum isolates infecting pregnant women are special in that parasites are able to sequester in vivo in the intervillous space and bind in vitro to chondroitin sulphate A (CSA) [3,4]. This placental accumulation of infected red blood cells (IRBCs) is associated with the low birth weight of the newborn [5]. Serum samples from exposed pregnant women recognize CSA-binding infected erythrocytes, independently of their geographic origin All this highlights the key role that VAR2CSA plays in the mechanism of PAM and the acquisition of protective immunity and clearly opens an excellent opportunity for the development of a vaccine against PAM [17]. The problem of polymorphism accounting for 10-30% variation between the different clinical isolates [18,19] represents a great challenge for designing a VAR2CSAbased vaccine
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