Absence of antigenic competition in Aotus monkeys immunized with Plasmodium falciparum DNA vaccines delivered as a mixture

Abstract

Aotus lemurinus lemurinus monkeys were immunized four times with one of three DNA plasmids expressing important Plasmodium falciparum blood stage vaccine candidate proteins or with a mixture containing all three vaccines. The three vaccines encoded sequences from apical merozoite antigen-1 (AMA-1), erythrocyte binding protein-175 (EBA-175) and merozoite surface protein-1 (MSP-1). Antigen-specific enzyme-linked immunosorbant assays (ELISAs) showed no significant differences in antibody titer induced to the three antigens by a single vaccine compared with the titer induced to that same antigen by the trivalent preparation. Results of immunofluorescent antibody assays against erythrocytes infected with asexual blood stage P. falciparum indicated that each of the three monovalent vaccines induced significant antibody responses to whole parasites. The trivalent vaccine mixture induced, after four immunizations, an antibody titer to whole parasites that was 3–12-fold higher than those induced by any of the single vaccines. The fourth immunization with the trivalent vaccine increased the mean antibody in IFAT by more than five-fold.