None of the malaria vaccines in development to target severe malaria in children are likely to be effective against placental malaria because of the underlying molecular mechanism that is unique to placental malaria.
VAR2CSA was identified by the team at the Center for Medical Parasitology at Copenhagen University. It is the main antigen candidate in the current efforts to develop a placental malaria vaccine. The ExpreS2 platform, with stable insect cell lines and non-lytic expression, offers reproducibility of production runs and more options for cultivation, such as perfusion. It is expected that these advantages will lead to reduced cost.
Structure of Pf VAR2CSA
The robustness of S2 cells and processes developed by the ExpreS2ion team facilitate transfer to cGMP manufacturing, shortening process transfer time and increasing the likelihood of success. CHO and other insect cells than S2 cells are less robust and more sensitive to process changes than S2 cells.
In this project, the ExpreS2 system was successfully used in screening to select the appropriate antigen variant. More than 30 variants were screened and tested in large scale in order to produce the needed malaria antigen within the given cost constraints. The protein was produced in the right conformation and at yields compatible with the development of a large-scale process.
Funding for clinical development
The clinical development of a VAR2CSA-based placental malaria vaccine is being funded by a FP7 grant, with the objective of producing the first placental malaria vaccine and performing the first clinical studies in humans. In parallel, the partners will prepare a field site and a protocol for a phase II study in African women.
Further reading about VAR2CSA’s role in placental malaria
- Salanti A, Staalsoe T, Lavstsen T, Jensen AT, Sowa MP, Arnot DE, Hviid L, Theander TG. Selective up-regulation of a single distinctly structured var gene in chondroitin sulphate A-adhering Plasmodium falciparum involved in pregnancy-associated malaria. Mol Microbiol. 2003 Jul;49(1):179-91.
- Salanti, A, Madeleine Dahlbäck, Louise Turner, Morten A. Nielsen, Lea Barfod, Pamela Magistrado, Anja T.R. Jensen, Thomas Lavstsen, Michael F. Ofori, Kevin Marsh, Lars Hviid, and Thor G. Theander. Evidence for the Involvement of VAR2CSA in Pregnancy-associated Malaria 2004 JEM vol. 200 no. 9 1197-1203.
- Khunrae P, Dahlbäck M, Nielsen MA, Andersen G, Ditlev SB, Resende M, Pinto VV, Theander TG, Higgins MK, Salanti A. Full-length recombinant Plasmodium falciparum VAR2CSA binds specifically to CSPG and induces potent parasite adhesion-blocking antibodies. J Mol Biol. 2010 Apr 2;397(3):826-34.
- Dyring, C. Development of a Pregnancy-associated malaria vaccines using the ExpreS2 insect cell expression system. Bioprocessing J. 2012, 11(3) : 14-19.
- de Jongh, W and Salanti A. Protein on the Fly. European Biopharmaceutical Journal 2012 58, 24-27.