Targeting Plasmodium falciparum chondroitin sulfate a ligand: A highly conserved malaria antigen with potential for pregnancy-associated malaria vaccine development

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This paper investigates a conserved antigen on Plasmodium falciparum's chondroitin sulfate A ligand, proposing it as a potential target for a pregnancy-associated malaria vaccine.

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Abstract

Background Pregnant women in malaria-endemic regions exhibit heightened susceptibility to Plasmodium falciparum infection due to accumulation of infected red blood cells (iRBCs) in the placenta. This is aided by the variant antigen 2 chondroitin sulfate A (VAR2CSA) protein which remains a target for pregnancy-associated malaria (PAM) vaccine studies. However, polymorphism in this antigen presents a significant challenge in developing broadly efficacious vaccines. This study explored PfCSA-L, a protein co-expressed and co-localized with VAR2CSA, as a potential alternative vaccine target due to its hypothesized role in PAM pathogenesis. Methods Sera and dried blood spots were collected from pregnant women attending antenatal care clinic at Webuye County Hospital, Western Kenya. P. falciparum infection status was confirmed by PCR. Recombinant PfCSA-L, expressed using a eukaryotic wheat germ cell-free system (WGCFS), was used to assess IgG antibody responses via ELISA. Results We observed a statistically significant increase in IgG levels as gestation advanced, suggesting potential exposure-driven antibody maturation against PfCSA-L. Primigravida women exhibited a trend toward higher anti-PfCSA-L antibody levels compared to multigravida during the second visit, possibly reflecting a more vigorous immune response during the first pregnancy. Genetic analysis of field parasite isolates revealed a high conservation of PfCSA-L at both DNA and protein levels. B-cell epitope prediction identified potential targets on the PfCSA-L surface within the conserved region. Conclusion These findings, coupled with the observed IgG response, further positions PfCSA-L as a promising vaccine candidate for PAM. However, further investigations are warranted to elucidate the functional role of anti-PfCSA-L antibodies and definitively validate PfCSA-L and/or the identified epitopes as potential PAM vaccine targets.
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last seen: 2026-05-20T01:45:00.602351+00:00