ChAd63-MVA-vectored blood-stage malaria vaccines targeting MSP1 and AMA1: assessment of efficacy against mosquito bite challenge in humans

摘要: The induction of cellular immunity, in conjunction with antibodies, may be essential for vaccines to protect against blood-stage infection the human malaria parasite Plasmodium falciparum. We have shown that prime-boost delivery P. falciparum antigens by chimpanzee adenovirus 63 (ChAd63) followed attenuated orthopoxvirus MVA is safe and immunogenic healthy adults. Here, we report on vaccine efficacy controlled delivered mosquito bites. were administered alone, or together (MSP1+AMA1), a pre-erythrocytic candidate (MSP1+ME-TRAP). In this first use coadministered ChAd63-MVA regimes, demonstrate immune interference whereby responses merozoite surface protein 1 (MSP1) are dominant over apical membrane antigen (AMA1) ME-TRAP. also show strong immunity MSP1 AMA1 safe, but does not impact growth rates blood. subset vaccinated volunteers, delay time diagnosis was observed sterilizing protection one volunteer coimmunized MSP1+AMA1—results consistent vaccine-induced pre-erythrocytic, rather than blood-stage, immunity. These data call into question utility T cell-inducing suggest focus should remain high-titer antibody susceptible targets.