Benoit GAMAIN

Information

Scientific interests and projects

The Severe Malaria Pathogenesis team was created on July 1st 2010 as an ATIP-Avenir team and renewed twice on January 1st 2014 and January 1st 2019 after HCERES evaluations as an INSERM-Paris Diderot university team.

We are focusing our research efforts on the identification and the deciphering of the molecular interactions involved in the Plasmodium falciparum infected erythrocytes cytoadhesion processes to develop vaccine and therapeutic strategies. We have various international collaborations in the malaria, red blood cells and the structural biology fields.

During the last years, we have been working mostly on the identification of the host-parasite interactions associated to placental malaria but also severe malaria. Our main discovery results in the structural and functional characterization of the parasite protein (var2CSA) responsible for P. falciparum infected erythrocytes (PEs) sequestration in the placenta. Our results have been the basis to initiate the PRIMALVAC vaccine development program that allowed the down-selection of the PRIMVAC vaccine candidate that has been tested in a Phase Ia/Ib vaccine clinical trial in France and Burkina-Faso.

Team members possess unique expertise such as:
- Studying P. falciparum infected erythrocytes adhesion mechanisms associated to severe malaria pathogenesis,
- Expressing difficult to express recombinant proteins to study their structure and function
- Vaccine development from bench to bedside
- Studying the post-translational modifications, notably the phosphorylation
- Developing the capacity to differentiate CD34+ Erythroid precursors in enucleated Red Blood Cells
- Modulating gene expression during Erythroid differentiation using lentivirus

Our team is working on the interaction between the malaria parasite and the host receptors as well as the impact of abnormal red cells on the parasite. Therefore, we could develop many interactions and develop projects with other ParaFrap members working on these different aspects.

Top 5 publications of last 5 years

1. Davies H., Belda H., Broncel M., Ye X., Bisson C., Introini V., Dorin-Semblat D., Semblat, J.P., Tibúrcio M., Gamain, B., Kaforou, M., Treeck M., An Exported Kinase Family Mediates Species-Specific Erythrocyte Remodelling and Virulence in Human Malaria. Nature Microbiol, 2019. In Press.

2. Dorin-Semblat D., Tetard M., Claes A., Semblat J.P., Dechavanne S., Fourati Z., Hamelin R., Armand F., Matesic G., Nunes-Silva S., Srivastava A., Gangnard S., Lopez-Rubio J.J., Moniatte M., Doerig C., Scherf A., and Gamain B., Phosphorylation of the VAR2CSA extracellular region is associated with enhanced adhesive properties to the placental receptor CSA. PLoS Biol, 2019. 17(6): p. e3000308. 10.1371/journal.pbio.3000308

3. Chene A., Gangnard S., Guadall A., Ginisty H., Leroy O., Havelange N., Viebig N.K., and Gamain B., Preclinical immunogenicity and safety of the cGMP-grade placental malaria vaccine PRIMVAC. EBioMedicine, 2019. 42: p. 145-156. 10.1016/j.ebiom.2019.03.010

4. Chene A., Gangnard S., Dechavanne C., Dechavanne S., Srivastava A., Tetard M., Hundt S., Leroy O., Havelange N., Viebig N.K., and Gamain B., Down-selection of the VAR2CSA DBL1-2 expressed in E. coli as a lead antigen for placental malaria vaccine development. NPJ vaccines, 2018. 3: p. 28. 10.1038/s41541-018-0064-6

5. Lennartz F., Adams Y., Bengtsson A., Olsen R.W., Turner L., Ndam N.T., Ecklu-Mensah G., Moussiliou A., Ofori M.F., Gamain B., Lusingu J.P., Petersen J.E., Wang C.W., Nunes- Silva S., Jespersen J.S., Lau C.K., Theander T.G., Lavstsen T., Hviid L., Higgins M.K., and Jensen A.T., Structure-Guided Identification of a Family of Dual Receptor-Binding PfEMP1 that Is Associated with Cerebral Malaria. Cell Host Microbe, 2017. 21(3): p. 403-414. 10.1016%2Fj.chom.2017.02.009