It showed promise in test-tube and animal experiments and in early-stage clinical trials, but returned disappointing results in recent human trials conducted in malaria-endemic countries.
Now, the NIAID scientists have improved on their original vaccine with a new candidate that delivers AMA1 protein together with part of a second parasite protein called RON2. In a natural infection, malaria parasites use the AMA1-RON2 complex to attach to and invade red blood cells. When injected into mice as a complex, the AMA1-RON2 vaccine prompted robust antibody production and protected the animals from a lethal form of mouse malaria. Moreover, when antibodies produced in response to AMA1-RON2 vaccine were administered to other, non-vaccinated mice, those animals received some protection from infection as well. Further analysis showed that the improved antibody response following AMA1-RON2 vaccination was due to an increased proportion of antibodies aimed directly at the AMA1-RON2 junction, which made them better at inhibiting parasite invasion.
The researchers note that this strategy of vaccination with the functional protein AMA1-RON2 complex could be tested in the next generation of human malaria vaccines. Such vaccines, which would contain multiple AMA1 sequences in complex with RON2, might induce antibodies targeted to a range of genetically diverse malaria parasites.