Multiple antigen constructs (MACs): induction of sterile immunity against sporozoite stage of rodent malaria parasites, Plasmodium berghei and Plasmodium yoelii

Abstract

We prepared multiple antigen constructs (MACs) using circumsporozoite (CS) protein-based B-epitopes from Plasmodium berghei, (PPPPNPND)2 and Plasmodium yoelii, (QGPGAP)3QG, along with a P. berghei T-helper epitope KQIRDSITEEWS. Mice were immunized with individual MACs in oil-in-water or water-in-oil vehicles containing block copolymer (P1005) and detoxified RaLPS (RaLPS) as well as other adjuvants. Sporozoite challenge results demonstrated that MACs in adjuvant could induce antibodies capable of active and passive protection. Water-in-oil vaccines induced the highest level of protection in mice immunized with either P. berghei or P. yoelii MACs. In a study aimed at co-eliciting immunity against P. berghei and P. yoelii, three immunizations with MACs induced protective antibodies against P. berghei but not P. yoelii parasite challenge. Therefore, it can be concluded that individually MACs are capable of inducing strong and protective immune responses to either species of rodent malaria, and that protection can be passively transferred. When MAC formulations were used together as a combined vaccine, P. berghei MACs induced a strong protective antibody response while P. yoelii MACs induced a weaker nonprotective response.