Antibodies to rhoptry-associated membrane antigen predict resistance to Plasmodium falciparum

Previously, we collected plasma from 143 male volunteers residing in an area of western Kenya where Plasmodium falciparum is holoendemic. Volunteers were cured of current malaria infection by use of drugs, blood was collected 2 weeks after treatment, and blood films were collected weekly for 18 weeks. We identified and pooled plasma from the 10 most resistant individuals (RP) and the 7 most susceptible individuals (SP) and used these pools in a differential screen of a P. falciparum cDNA expression library. We screened 550,000 clones and identified 7 clones that were uniquely recognized by RP but not by SP. Two clones encoded a C-terminal region polypeptide from rhoptry-associated membrane antigen (RAMA-pr), a recently described RAMA. We measured anti-RAMA-pr antibody levels in plasma obtained 2 weeks after treatment. Individuals with detectable immunoglobulin G1 anti-RAMA-pr (n = 24) had fewer positive blood films (odds ratio, 1.7 [95% confidence interval, 1.21-2.44]; P < .003), 43% lower density of parasitemia (P < .02), and prolonged time to reinfection (P < .0027), compared with individuals without detectable antibody levels (n = 115), after known determinants of resistance were accounted for. In summary, RAMA-pr is a rationally identified vaccine candidate that is preferentially recognized by antibodies produced by humans with a high level of naturally acquired resistance to P. falciparum infection.