Naturally Acquired Antibodies Specific for Plasmodium falciparum Reticulocyte-Binding Protein Homologue 5 Inhibit Parasite Growth and Predict Protection From …
TM Tran, A Ongoiba, J Coursen… - The Journal of …, 2014 - academic.oup.com
The Journal of infectious diseases, 2014•academic.oup.com
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 …
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 …
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.
Oxford University Press