A malaria vaccine protects Aotus monkeys against virulent Plasmodium falciparum infection

The Plasmodium falciparumprotein, apical membrane antigen 1forms a complex with another parasite protein, rhoptryneck protein 2, to initiate junction formation with the erythrocyte and is essential for merozoite invasion during the blood stage of infection. Consequently, apical membrane antigen 1has been a target of vaccine development but vaccination with apical membrane antigen 1alone in controlled human malaria infections failed to protect and showed limited efficacy in field trials. Here we show that vaccination with AMA1–RON2L complex in Freund’s adjuvantprotects Aotus monkeys against a virulent Plasmodium falciparuminfection. Vaccination with AMA1 alone gave only partial protection, delaying infection in one of eight animals. However, the AMA1–RON2L complex vaccine completely protected four of eight monkeys and substantially delayed infection (>25 days) in three of the other four animals. Interestingly, antibodies from monkeys vaccinated with the AMA1–RON2L complex had significantly higher neutralizing activity than antibodies from monkeys vaccinated with AMA1 alone. Importantly, we show that antibodies from animals vaccinated with the complex have significantly higher neutralization activity against non-vaccine type parasites. We suggest that vaccination with the AMA1–RON2L complex induces functional antibodies that better recognize AMA1 as it appears complexed with RON2 during merozoite invasion. These data justify progression of this next generation AMA1 vaccine towards human trials. A vaccine targeting a protein complex that allows malaria-causing parasite to enter red blood cells has been produced. Malaria caused by the parasite Plasmodium falciparumis an oft-deadly infectious disease without an effective vaccine. A team of researchers at the National Institutes of Health led by Prakash Srinivasan, currently at the Johns Hopkins Malaria Research Institute, United States, demonstrated the efficacy of a vaccine candidate that works by priming a host’s immune system to a parasitic protein complex required to form a junction with red blood cells, allowing entry and proliferation of the pathogen. The group’s vaccine conferred more effective protection in monkeys than prior candidates that targeted only one component of the parasitic protein complex. This research warrants a closer look into how this candidate, and others targeting the protein complex, can be used to prevent malaria in humans.