Combined vaccination with different type vaccines of Plasmodium falciparum AMAl

Objective: To explore the potential of combined vaccination using DNA vaccine, recorabinant vaccinia virus vaccine and recombinant protein vaccine in inducing protective antibodies to malaria antigen AMA1. Methods: AMA1 ectodomain encoding gene was amplified by PCR from the genome of YN strain of Plasmodium falciparum. DNA vaccine plasmid VR1020/E(vaccine D), recombinant modified vaccinia virus Ankara rMVA/E(vaccine V) and prokaryotic expressed AMA1 ectodomain protein E(vaccine P) were constructed and prepared. BALB/c mice were primed two times with vaccine D only or together with GM-CSF expressing plasmid at O w and 3 w, at 9 w they were given a booster dose of vaccine V or vaccine P, at 15 w two groups received another booster with different type vaccines. New Zealand rabbits were immunized under vaccine D-V approach. The titers of IgG in mice sera and the IgG subtypes were determined by ELISA. The ability of immune sera in inhibiting plasmodium merozoites invasion were evaluated. Results: AMA1 specific antibodies in vaccine D primed mice were greatly enhanced after vaccination with vaccine V or vaccine P, their IgG levels increased by 15 to 137 times. The antibody responses can be promoted in mice immunization by vaccine D-V with additional pcDNA3/GM-CSF. Obvious antibodies were induced in rabbits under vaccine D-V approach. Both mice and rabbit immune sera showed remarkable inhibitory effect on the invasion of merozoites into RBCs. Conclusion: It is a potent way to induce protective antibodies to the intraerythrocytic malaria parasites by combined vaccination of DNA vaccine, recombinant MVA vaccine and recombinant protein vaccine.