Naturally acquired antibodies specific for Plasmodium falciparum reticulocyte-binding protein homologue 5 inhibit parasite growth and predict protection from malaria.

Tuan M Tran, Aissata Ongoiba, Jill Coursen, Cecile Crosnier, Ababacar Diouf, Chiung-Yu Huang, Shanping Li, Safiatou Doumbo, Didier Doumtabe, Younoussou Kone, Aboudramane Bathily, Seydou Dia, Moussa Niangaly, Charles Dara, Jules Sangala, Louis H Miller, Ogobara K Doumbo, Kassoum Kayentao, Carole A Long, Kazutoyo MiuraGavin J Wright, Boubacar Traore, Peter D Crompton

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)789-798
Number of pages10
JournalThe Journal of Infectious Diseases
Issue number5
Early online date16 Oct 2013
Publication statusPublished - 1 Mar 2014

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