1. Naturally acquired antibodies specific for Plasmodium falciparum reticulocyte-binding protein homologue 5 inhibit parasite growth and predict protection from malaria.
- Author
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Tran, Tuan, Ongoiba, Aissata, Coursen, Jill, Crosnier, Cecile, Diouf, Ababacar, Huang, Chiung-Yu, Li, Shanping, Doumbo, Safiatou, Doumtabe, Didier, Kone, Younoussou, Bathily, Aboudramane, Dia, Seydou, Niangaly, Moussa, Dara, Charles, Sangala, Jules, Miller, Louis, Doumbo, Ogobara, Kayentao, Kassoum, Long, Carole, Miura, Kazutoyo, Wright, Gavin, Traore, Boubacar, and Crompton, Peter
- Subjects
Plasmodium falciparum ,RH5 ,blood-stage immunity ,endemic population ,malaria ,prospective cohort study ,Adolescent ,Adult ,Antibodies ,Protozoan ,Carrier Proteins ,Child ,Child ,Preschool ,Female ,Humans ,Immunoglobulin G ,Infant ,Malaria Vaccines ,Malaria ,Falciparum ,Male ,Placenta ,Plasmodium falciparum ,Pregnancy ,Reticulocytes ,Young Adult - 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.
- Published
- 2014