A Plasmodium Vivax Plasmid DNA- And Adenovirus-Vectored Malaria Vaccine Encoding Blood-Stage Antigens AMA1 and MSP1 42 in a Prime/Boost Heterologous Immunization Regimen Partially Protects Aotus Monkeys Against Blood-Stage Challenge

Malaria is caused by parasites of the genus , which are transmitted to humans by the bites of mosquitoes. After the elimination of , it is predicted that will remain an important cause of morbidity and mortality outside Africa, stressing the importance of developing a vaccine against malaria. In this study, we assessed the immunogenicity and protective efficacy of two antigens, apical membrane antigen 1 (AMA1) and the 42-kDa C-terminal fragment of merozoite surface protein 1 (MSP1) in a plasmid recombinant DNA prime/adenoviral (Ad) vector boost regimen in monkeys. Groups of 4 to 5 monkeys were immunized with plasmid DNA alone, Ad alone, prime/boost regimens with each antigen, prime/boost regimens with both antigens, and empty vector controls and then subjected to blood-stage challenge. The heterologous immunization regimen with the antigen pair was more protective than either antigen alone or both antigens delivered with a single vaccine platform, on the basis of their ability to induce the longest prepatent period and the longest time to the peak level of parasitemia, the lowest peak and mean levels of parasitemia, the smallest area under the parasitemia curve, and the highest self-cure rate. Overall, prechallenge MSP1 antibody titers strongly correlated with a decreased parasite burden. Nevertheless, a significant proportion of immunized animals developed anemia. In conclusion, the plasmid DNA/Ad serotype 5 vaccine encoding blood-stage parasite antigens AMA1 and MSP1 in a heterologous prime/boost immunization regimen provided significant protection against blood-stage challenge in monkeys, indicating the suitability of these antigens and this regimen for further development.