Towards a vaccine against pregnancy-associated malaria

Ndam, Nicaise Tuikue; Deloron, Philippe

doi:10.1051/parasite/2008153515

Cited by 14 publications

(6 citation statements)

References 63 publications

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“…Immunity directed against VAR2CSA develops naturally with successive pregnancies and appears to protect against adverse birth outcomes 11 . Therefore, vaccination against VAR2CSA could be an effective way to reduce the effect of adverse outcomes from PAM 14 – 18 .…”

Section: Introductionmentioning

confidence: 99%

Increased risk of low birth weight in women with placental malaria associated with P. falciparum VAR2CSA clade

Patel

Hathaway²,

Parobek

et al. 2017

Sci Rep

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Pregnancy associated malaria (PAM) causes adverse pregnancy and birth outcomes owing to Plasmodium falciparum accumulation in the placenta. Placental accumulation is mediated by P. falciparum protein VAR2CSA, a leading PAM-specific vaccine target. The extent of its antigen diversity and impact on clinical outcomes remain poorly understood. Through amplicon deep-sequencing placental malaria samples from women in Malawi and Benin, we assessed sequence diversity of VAR2CSA’s ID1-DBL2x region, containing putative vaccine targets and estimated associations of specific clades with adverse birth outcomes. Overall, var2csa diversity was high and haplotypes subdivided into five clades, the largest two defined by homology to parasites strains, 3D7 or FCR3. Across both cohorts, compared to women infected with only FCR3-like variants, women infected with only 3D7-like variants delivered infants with lower birthweight (difference: −267.99 g; 95% Confidence Interval [CI]: −466.43 g,−69.55 g) and higher odds of low birthweight (<2500 g) (Odds Ratio [OR] 5.41; 95% CI:0.99,29.52) and small-for-gestational-age (OR: 3.65; 95% CI: 1.01,13.38). In two distinct malaria-endemic African settings, parasites harboring 3D7-like variants of VAR2CSA were associated with worse birth outcomes, supporting differential effects of infection with specific parasite strains. The immense diversity coupled with differential clinical effects of this diversity suggest that an effective VAR2CSA-based vaccine may require multivalent activity.

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Section: Introductionmentioning

confidence: 99%

Increased risk of low birth weight in women with placental malaria associated with P. falciparum VAR2CSA clade

Patel

Hathaway²,

Parobek

et al. 2017

Sci Rep

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“…Identification of a distinct PfEMP1 variant, VAR2CSA as the dominant surface antigen and a clinically important target for a protective immune response to malaria in pregnancy has raised hope. 187 …”

Section: Introductionmentioning

confidence: 99%

A brief review on features of falciparum malaria during pregnancy

Manirakiza

Serdouma

Ngbale

et al. 2017

J Public Health Afr

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Malaria in pregnancy is a serious public health problem in tropical areas. Frequently, the placenta is infected by accumulation of Plasmodium falciparum-infected erythrocytes in the intervillous space. Falciparum malaria acts during pregnancy by a range of mechanisms, and chronic or repeated infection and co-infections have insidious effects. The susceptibility of pregnant women to malaria is due to both immunological and humoral changes. Until a malaria vaccine becomes available, the deleterious effects of malaria in pregnancy can be avoided by protection against infection and prompt treatment with safe, effective antimalarial agents; however, concurrent infections such as with HIV and helminths during pregnancy are jeopardizing malaria control in sub-Saharan Africa.

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“…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]. However, the problem of polymorphism accounting for 10-30% variation between the different clinical isolates [18,19] represents a great challenge for designing a VAR2CSA-based vaccine.…”

Section: Introductionmentioning

confidence: 99%

Plasmodium falciparum population dynamics in a cohort of pregnant women in Senegal

Guitard

Andersen

Ermont

et al. 2010

Malar J

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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.

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Towards a vaccine against pregnancy-associated malaria

Cited by 14 publications

References 63 publications

Increased risk of low birth weight in women with placental malaria associated with P. falciparum VAR2CSA clade

Increased risk of low birth weight in women with placental malaria associated with P. falciparum VAR2CSA clade

A brief review on features of falciparum malaria during pregnancy

Plasmodium falciparum population dynamics in a cohort of pregnant women in Senegal

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