Malaria is caused by parasites, which are transmitted by mosquito bites. Of the five parasites capable of infecting humans, Plasmodium falciparum and Plasmodium vivax, are responsible for over 95% of all infections worldwide. P. falciparum causes the most severe form of malaria, Malaria tropica, accounting for the vast majority of fatal cases. P. vivax, the most widespread parasite (e.g. responsible for more than 50% of malaria cases in India and Brazil) poses a particular problem, as dormant forms of the parasite can remain in the body for years and can induce repeated outbreaks of the disease in the absence of new transmission. Sumaya’s goal is the development of vaccines against both, P. falciparum and P. vivax infections, whereby the first focus is on vaccines against P. falciparum.

Sumaya’s vaccines aim at alerting the human immune system towards two crucial stages of the parasite’s infectious cycle: the liver and the blood stage. This is a key competitive differentiator against most existing approaches.

The basis of Sumaya’s vaccine candidates is the large surface exposed, membrane anchored protein of “merozoites”, the blood cell invading form of the parasite. This protein, “Merozoite Surface Protein 1” (MSP-1), plays a crucial role during invasion of blood cells by the parasite. Its overall structure is remarkably well conserved among P. falciparum isolates from different parts of the world. It is initially synthesized in infected liver cells, the first target of the parasite after the infecting bite of a parasite-carrying mosquito. Massive multiplication of the parasite in the liver and its release into the blood stream leads to the blood stage of the infection, where parasites infect red blood cells. Here they multiply again, subsequently killing the host cells and re-infecting new red blood cells. It is this blood stage which causes all pathophysiological symptoms frequently deadly in unprotected, “naive” individuals.

The candidacy of MSP-1 as a highly promising antigen for a vaccine candidate is well supported by epidemiological field studies in West Africa, experiments in various animal models and studies with parasite cultures in vitro. These studies have revealed in particular, that (i) antibodies against MSP-1 correlate with a reduced risk of re-infection in West African adolescents, (ii) MSP-1 specific immune responses are elicited at the liver (cellular response) as well as at the blood stage (antibody response), (iii) antibodies raised against the recombinant MSP-1 vaccine candidate can efficiently inhibit the growth of different parasite strains in vitro, (iv) the epitopes which elicit the broad spectrum of MSP-1 specific immune responses are distributed throughout the large, 200kDa protein making MSP-1 a large target for immune attack.

These make full size MSP-1 a prime vaccine candidate, which is multivalent, i.e. it is effective against many parasite strains, as well as “multistage”, i.e. it interferes with the parasite’s infectious cycle at several levels.

Particularly in these aspects MSP-1 compares favorably to other candidate antigens or combinations thereof, which have already been evaluated clinically, or are currently under clinical investigation.