Antibodies to Variant Surface Antigens ofPlasmodium falciparum–Infected Erythrocytes Are Associated with Protection from Treatment Failure and the Development of Anemia in Pregnancy

Abstract

Background In pregnancy associated malaria (PAM), Plasmodium falciparum infected erythrocytes (IEs) express variant surface antigens (VSA-PAM) that evade existing immunity and mediate placental sequestration. Antibodies to VSA-PAM develop with gravidity and block placental adhesion or opsonise IEs for phagocytic clearance, protecting women from anemia and low birth weight Methods and findings Using sera from 141 parasitemic pregnant Malawian women enrolled in a randomized trial of antimalarials and VSA-PAM-expressing CS2 IEs, we quantitated levels of IgG to VSA-PAM by flow cytometry and opsonizing antibodies by measuring uptake of IEs by THP1 promonocytes. After controlling for gravidity and antimalarial treatment, IgG against VSA-PAM was associated with decreased anemia at delivery (OR=0.66, 95% confidence interval [CI] 0.46, 0.93; P=0.018) and weakly associated with decreased parasitological failure (OR=0.78; 95% CI, 0.60, 1.03; P=0.075), especially re-infection (OR=0.73; CI, 0.53,1.01; P=0.057). Opsonizing antibodies to CS2 IE were associated with less maternal anemia. (OR=0.31, 95% CI, 0.13, 0.74; P=0.008) and treatment failure (OR=0.48; 95% CI, 0.25, 0.90; P=0.023), primarily due to recrudescent infection (OR=0.49; 95% CI, 0.21, 1.12; P=0.089). Conclusion Both IgG antibody to VSA-PAM and opsonizing antibody, a functional measure of immunity correlate with parasite clearance and less anemia in pregnancy malaria.

IgG against Plasmodium falciparum variant surface antigens and growth inhibitory antibodies in Mozambican children receiving intermittent preventive treatment with sulfadoxine-pyrimethamine

“…Our choice of a pool of three P. falciparum isolates (MOZ2, R29 and E8B) was believed to give reasonable representation of the variants expressed in the population. Other studies in different age groups have found variable results; some reported associations between VSA antibodies and protection but others have not (Marsh et al 1989;Bull et al 1998;Giha et al 2000;Dodoo et al 2001;Feng et al 2009), therefore the role of VSA antibody responses in protection in infancy and early childhood needs to be further investigated.…”

Immune responses during gestational malaria: a review of the current knowledge and future trend of research

“…This immunity is acquired as a result of antigenic stimulation through repeated parasite infections from early childhood onwards [109] but exposition to infection during fetal stages lead to impairment of memory responses and increased rates of infection later in life [110]. Susceptibility to malaria during pregnancy has been attributed to lack of antibodies able to block the binding of P. falciparum to CSA in the placenta [111] and to facilitate opsonic uptake by phagocytes [112][113][114]. The CSA adhesion phenotype is specific to placental parasites and it has been linked to the expression of a unique var gene (var2csa) [80,82].…”

Influence of Intermittent Preventive Treatment on Antibodies to VAR2CSA in Pregnant Cameroonian Women

“…[7][8][9][10] Fortunately, antibodies (Abs) to placental-binding IE reduce sequestration and improve pregnancy outcomes. [11][12][13][14][15][16][17] Abs to VAR2CSA are acquired over successive pregnancies that reduce the risk of placental malaria (PM). 7,12,15 Intermittent preventive treatment (IPT) with sulfadoxinepyrimethamine (SP) and insecticide-treated bed nets (ITN) are the recommended standard of care for preventing malaria during pregnancy in areas with moderate to high transmission.…”