Assessment of the efficacy of a VAR2CSA based vaccine to prevent malaria in pregnant women

Start date: 30 September, 2009 End date: 29 March, 2013 Project type: Smaller projects: PhD Project code: 09-003KU Countries: Tanzania Thematic areas: Health, Lead institution: Tanga Medical Research Centre, University of Copenhagen (UCPH)/Rigshospitalet, Centre for Medical Parasitology (CMP), University of Copenhagen (UCPH)/Rigshospitalet, Denmark, Total grant: 2,131,835 DKK Contact person: Sisse Bolm Ditlev

Description

Malaria is the cause of severe maternal anaemia and is responsible for about one third of preventable low birth weight babies. It contributes to the deaths of an estimated 10,000 pregnant women and up to 200,000 infants each year in Afica alone. At the Centre for Medical Parasitology (CMP), University of Copenhagen we have identified the protein, VAR2CSA which is the major virulence factor in malaria during pregnancy, and we have defined a smaller part of VAR2CSA to use in a vaccine (the DBL4 domain). The objective of this PhD study is to refine and produce a DBL4 protein, which can be used as a vaccine protecting pregnant women against malaria. The researcher will produce a number of different DBL4 proteins and induce antibodies in rats. In collaboration with Senior Scientist Md, PhD John Lusingu from the National Institute for Medical Research, Tanga, Tanzania and Post. doc. Pamela Magistrado, the researcher will test the efficacy of the animal-induced antibodies with respect to inhibit parasite binding to placental tissue receptors. The project will take place at the Centre for Medical Parasitology (CMP) at the University of Copenhagen and in co-operation with the FP7 STOPPAM programme as well as a DANIDA project (87/08/KU) and in collaboration with the National Institute for Medical Research in Tanga, Tanzania. The final part of the PhD will be to transfer to the chosen vaccine antigen to a platform which is suitable for high scale protein production for clinical trials.

Outputs

Annual Report 2012:

Protection to the clinical symptoms of placental malaria is acquired along parity suggesting that it is feasible to make a vaccine against placental malaria. In this project we have produced a single domain of the parasite-protein used for binding to the placenta to induce antibodies in rats. This protein can induce antibodies in rats that are able to inhibit parasites-binding to the placental receptor even though this domain is not a part of the specific binding domain. The binding-region of the parasite to the receptor has now been identified and is another vaccine candidate. This new candidate is beeing refined to be used in clinical trials the coming years. The aim is to make a binding-inhibitory vaccine that induces antibodies in the women that prevents the parasite binding to the placental receptor. The results from this project have provided valuable information for the selection of a VAR2CSA vaccine construct and for the further optimization before going into clinical trials.