VAR2CSA DBL1-2: A Lead Antigen for Malaria Vaccine Development

12Jungle fever caused by Plasmodium constitutes a noteworthy medical issue is as yet a standout amongst the most widely recognized dangerous irresistible maladies on the planet. In 2016, the worldwide count of jungle fever achieved 216 million cases and 445,000 passing, a substantial larger part of them coming about because of Plasmodium falciparum infection.1 Individuals living in high P. falciparum transmission settings step by step obtain insusceptibility to the most serious clinical signs of the contamination. Every year, PM is in charge of 20% of stillbirths in sub-Saharan Africa, 11% of every infant passing in sub-Saharan Africa, and 10,000 maternal passing all around.

Over 50 million women are exposed to the risk of malaria during pregnancy every year. Malaria during pregnancy is a leading global cause of maternal morbidity and adverse pregnancy outcomes. Adhesion of infected erythrocytes to placental chondroitin-4-sulfate (CSA) has been linked to outcome of placental malaria. Accumulated evidence strongly supports VAR2CSA as the leading placental malaria vaccine candidate.13

Recombinant proteins encompassing the VAR2CSA high affinity CSA binding site have been generated, and their activity as immunogens that elicit functional (inhibitory) and cross-reactive antibodies against CSA-binding parasites assessed.14

The expression of His-tagged proteins was compared in four different expression systems and their capacity to bind specifically to CSA was analysed. CHO cells and E. coli Shuffle cells were the two expression systems able to express some of the recombinant proteins in reasonable amounts. Larger analytical scale production of DBL1x-2× (3D7) and DBL3x-4ε (FCR3) best expressed in CHO and E. coli Shuffle cells were performed.

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Purified proteins were administered to rats either alone or adjuvant with human approved adjuvants. Analysis of the functionality and cross-reactivity of the induced antibodies allowed us to down-select the DBL1x-2(3D7) expressed in E. coli Shuffle cells as the best antigen to be transitioned to further clinical development in order to protect future pregnant women living in malaria endemic areas against the severe clinical outcomes of placental malaria.

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