The first line of business is the development of a Vaccine against Plasmodium vivax malaria.
P. vivax is the most widely distributed human malaria parasite and responsible each year for 100-300 million clinical cases including severe disease and death. Moreover, it is estimated that close to 60 million tourists, business people, military personnel and government employees travel to endemic regions each year. In spite of its Public Health importance and the huge socio-economical lost associated with vivax malaria, vaccine development against this species lags hugely behind that of P. falciparum, the most virulent species inflicting mostly sub-Saharan Africa, As immunity in malaria is species-specific, vaccines against P. falciparum will not be effective against P. vivax
Exosomes are 30-100-nm membrane vesicles formed by endocytosis of segments of the plasma membrane. The internalized segment generates multivesicular bodies (MVBs) containing small vesicles that are released as exosomes following fusion of the MVBs with the plasma membrane. Exosomes were originally described in reticulocytes where they allow remodelling of the plasma membrane in the maturation to erythrocytes by eliminating specific proteins. Remarkably, reticulocytes are the cells preferentially, if not exclusively, invaded by Plasmodium vivax. We thus hypothesized that reticulocyte-derived exosomes (rex) in vivax infections, in addition to their role as cargo-disposable machinery, should contain parasite proteins and that these nanovesicles could be used as novel platform and vaccine against P. vivax.
Proof-of-concept was obtained with a rodent malaria model that infects reticulocytes and in which immunization of animals with rex in combination with CpG conferred full and long-lasting protection to animals upon a lethal challenge (PCT/EP2010/070800).