Induction of protective antibodies in Saimiri monkeys by immunization with a multiple antigen construct (MAC) containing the Plasmodium vivax circumsporozoite protein repeat region and a universal T helper epitope of tetanus toxin

Previous attempts in inducing protective immunity against Plasmodium vivax in human volunteers and nonhuman primates with recombinant circumsporozoite (CS) proteins have been unsuccessful, largely due to the failure of generating antibodies against the protective B epitope AGDR in the CS protein repeat region. We report here an immunization study in Saimiri monkeys with a multiple antigen construct (MAC) containing the P. vivax CS protein repeat region and a T helper epitope of tetanus toxin formulated in different adjuvants. Monkeys immunized three times with MAC in copolymer P1005, copolymer P1005 plus RaLPS, or MF-75 had titers of antibodies against CS repeat, sporozoites and the protective B epitope AGDR significantly higher than those immunized with MAC in alum or PBS (P 0.05; 21527 vs 196 for the rechallenge, P 0.05; r=0.60 for the rechallenge, P<0.05) and negatively correlated with the peak parasitemia (r=−0.39 for the first challenge, P<0.05; r=−0.50 for the rechallenge, P<0.05). The results suggested that when combined with the use of potent adjuvants and T helper epitopes, MAC subunit vaccines may potentially offer protection against malaria infection.