Characterization of the role of secreted small cysteine-rich protein (CSS) in Plasmodium berghei sporozoite transmission

The development of a malaria vaccine has been one of the greatest challenges in the biomedical sciences in recent decades. The problem lies in the fact that Plasmodium, the etiological agent, is a very polymorphic parasite that has escape mechanisms that allow it to evade the host’s immune system. Currently, there is only one vaccine for malaria caused by P. falciparum, which causes the serious illness. In the case of P. vivax, the most prevalent parasite in Latin America, the possibility of a vaccine is even more challenging, since this species of parasite is difficult to maintain in vitro, which makes it difficult to search for new targets and tests of promissory antigens. Invasion of the erythrocyte by the merozoite is an important step in the development of the Plasmodium life cycle. As the interruption of this process prevents the progression of the disease, it represents an interesting approach for the development of vaccines against Malaria. The RH5-RIPR-CyRPA invasion complex identified in P. falciparum has aroused particular interest due to its appearance as a promising antigen for the creation of erythrocytic phase vaccines. Unfortunately, Rh5 seems to be specific to P. falciparum and P. reichenowi (parasites of the Laverania clade) since orthologs have not been found in other Plasmodium species. In the case of CyRPA, although orthologs have been found in other species, it does not interact with the merozoite invasion complex of P. knowlesi. On the other hand, RIPR is conserved and has orthologs in species such as P. vivax, P. knowlesi and P. berghei, suggesting that the RIPR-Rh5 functional pathway may also be conserved and that the role played by PfRh5 is fulfilled by another protein in the other species of Plasmodium. The CSS protein (Cysteine-rich Small Secreted) was recently described and it is known that it interacts with RIPR and PTRAMP in P. knowlesi, and in the laboratory, it was found that CSS interacts with RIPR in P. berghei. Recently it was observed that antibodies against the complex of proteins that interact with RIPR, inhibit the invasion of the host cells by the merozoites, and in this way these proteins represent interesting targets for the creation of vaccines.

Project details

Basic Science

Mar 2023 — Feb 2024

Brazil

Plasmodium knowlesi