Construction and evaluation of a multistage combination vaccine against malaria.

Due to the complex life cycle and high antigenic diversity of the malaria parasite, a multistage vaccine may be necessary for optimal protection against the disease. Our previous studies demonstrated that a blood-stage recombinant protein PfCP-2.9 has significant potential for vaccine development and is currently in human clinical trials. This study constructed two recombinant antigens derived from the Plasmodium falciparum CSP, designated PfCSP-C and PfCSP-RC. They were expressed as secreted proteins at high yield (1-3 g/l) in Pichia pastoris and purified by a two-step purification procedure. There was no evidence of antigen competition in mice and rabbits co-immunized with the pre-erythrocytic antigens and PfCP-2.9. Moreover, the immune sera recognized both the blood-stage parasite and sporozoite, and interacted with the NANP repeats of PfCSP. Rabbits antisera to combination antigens strongly inhibited blood-stage parasite growth in vitro. These results suggest that the recombinant antigens are potential candidates for multistage combination vaccines against malarial parasite.