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  • Title: Naturally acquired antibodies specific for Plasmodium falciparum reticulocyte-binding protein homologue 5 inhibit parasite growth and predict protection from malaria.
    Author: Tran TM, Ongoiba A, Coursen J, Crosnier C, Diouf A, Huang CY, Li S, Doumbo S, Doumtabe D, Kone Y, Bathily A, Dia S, Niangaly M, Dara C, Sangala J, Miller LH, Doumbo OK, Kayentao K, Long CA, Miura K, Wright GJ, Traore B, Crompton PD.
    Journal: J Infect Dis; 2014 Mar 01; 209(5):789-98. PubMed ID: 24133188.
    Abstract:
    BACKGROUND: Plasmodium falciparum reticulocyte-binding protein homologue 5 (PfRH5) is a blood-stage parasite protein essential for host erythrocyte invasion. PfRH5-specific antibodies raised in animals inhibit parasite growth in vitro, but the relevance of naturally acquired PfRH5-specific antibodies in humans is unclear. METHODS: We assessed pre-malaria season PfRH5-specific immunoglobulin G (IgG) levels in 357 Malian children and adults who were uninfected with Plasmodium. Subsequent P. falciparum infections were detected by polymerase chain reaction every 2 weeks and malaria episodes by weekly physical examination and self-referral for 7 months. The primary outcome was time between the first P. falciparum infection and the first febrile malaria episode. PfRH5-specific IgG was assayed for parasite growth-inhibitory activity. RESULTS: The presence of PfRH5-specific IgG at enrollment was associated with a longer time between the first blood-stage infection and the first malaria episode (PfRH5-seropositive median: 71 days, PfRH5-seronegative median: 18 days; P = .001). This association remained significant after adjustment for age and other factors associated with malaria risk/exposure (hazard ratio, .62; P = .02). Concentrated PfRH5-specific IgG purified from Malians inhibited P. falciparum growth in vitro. CONCLUSIONS: Naturally acquired PfRH5-specific IgG inhibits parasite growth in vitro and predicts protection from malaria. These findings strongly support efforts to develop PfRH5 as an urgently needed blood-stage malaria vaccine. CLINICAL TRIALS REGISTRATION: NCT01322581.
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