Progress and Insights Toward an Effective Placental Malaria Vaccine

In areas where Plasmodium falciparum transmission is endemic, clinical immunity against malaria is progressively acquired during childhood and adults are usually protected against the severe clinical consequences of the disease. Nevertheless, pregnant women, notably during their first pregnancies, are susceptible to placental malaria and the associated serious clinical outcomes. Placental malaria is characterized by the massive accumulation of P. falciparum infected erythrocytes and monocytes in the placental intervillous spaces leading to maternal anaemia, hypertension, stillbirth and low birth weight due to premature delivery, and foetal growth retardation. Remarkably, the prevalence of placental malaria sharply decreases with successive pregnancies. This protection is associated with the development of antibodies directed towards the surface of P. falciparum-infected erythrocytes from placental origin. Placental sequestration is mediated by the interaction between VAR2CSA, a member of the P. falciparum erythrocyte membrane protein 1 family expressed on the infected erythrocytes surface, and the placental receptor chondroitin sulfate A. VAR2CSA stands today as the leading candidate for a placental malaria vaccine. We recently reported the safety and immunogenicity of two VAR2CSA-derived placental malaria vaccines (PRIMVAC and PAMVAC), spanning the chondroitin sulfate A-binding region of VAR2CSA, in both malaria-naïve and P. falciparum-exposed non-pregnant women in two distinct Phase I clinical trials (ClinicalTrials.gov, NCT02658253 and NCT02647489). This review discusses recent advances in placental malaria vaccine development, with a focus on the recent clinical data, and discusses the next clinical steps to undertake in order to better comprehend vaccine-induced immunity and accelerate vaccine development.

Immobilization of Chondroitin Sulfate A onto Monolithic Epoxy Silica Column as a New Chiral Stationary Phase for High-Performance Liquid Chromatographic Enantioseparation

Chondroitin sulfate A was covalently immobilized onto a monolithic silica epoxy column involving a Schiff base formation in the presence of ethylenediamine as a spacer and evaluated in terms of its selectivity in enantioseparation. The obtained column was utilized as a chiral stationary phase in enantioseparation of amlodipine and verapamil using a mobile phase consisting of 50 mM phosphate buffer pH 3.5 and UV detection. Sample dilution by organic solvents (preferably 25% v/v acetonitrile-aqueous solution) was applied to achieve baseline enantioresolution (Rs > 3.0) of the individual drug models within 7 min, an excellent linearity (R2 = 0.999) and an interday repeatability of 1.1% to 1.8% RSD. The performance of the immobilized column for quantification of racemate in commercial tablets showed a recovery of 86–98% from tablet matrices. Computational modeling by molecular docking was employed to investigate the feasible complexes between enantiomers and the chiral selector.