title: Naturally acquired antibodies specific for Plasmodium falciparum reticulocyte-binding protein homologue 5 inhibit parasite growth and predict protection from malaria.
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.
  
  
  BACKGROUND
  NCT01322581.
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland.
authors.forename: Tuan M
authors.initials: TM
authors.lastname: Tran
authors.forename: Aissata
authors.initials: A
authors.lastname: Ongoiba
authors.forename: Jill
authors.initials: J
authors.lastname: Coursen
authors.forename: Cecile
authors.initials: C
authors.lastname: Crosnier
authors.forename: Ababacar
authors.initials: A
authors.lastname: Diouf
authors.forename: Chiung-Yu
authors.initials: CY
authors.lastname: Huang
authors.forename: Shanping
authors.initials: S
authors.lastname: Li
authors.forename: Safiatou
authors.initials: S
authors.lastname: Doumbo
authors.forename: Didier
authors.initials: D
authors.lastname: Doumtabe
authors.forename: Younoussou
authors.initials: Y
authors.lastname: Kone
authors.forename: Aboudramane
authors.initials: A
authors.lastname: Bathily
authors.forename: Seydou
authors.initials: S
authors.lastname: Dia
authors.forename: Moussa
authors.initials: M
authors.lastname: Niangaly
authors.forename: Charles
authors.initials: C
authors.lastname: Dara
authors.forename: Jules
authors.initials: J
authors.lastname: Sangala
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
authors.forename: Kassoum
authors.initials: K
authors.lastname: Kayentao
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Miura
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Wright
authors.forename: Boubacar
authors.initials: B
authors.lastname: Traore
authors.forename: Peter D
authors.initials: PD
authors.lastname: Crompton
mesh_terms: D000293:Adolescent; D000328:Adult; D000913:Antibodies, Protozoan / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007223:Infant; D017780:Malaria Vaccines / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology / Q000635:transmission; D008297:Male; D010920:Placenta / Q000276:immunology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology*; D011247:Pregnancy; D012156:Reticulocytes / Q000276:immunology / Q000469:parasitology; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D002352:Carrier Proteins; D007074:Immunoglobulin G; D017780:Malaria Vaccines; C531020:RH5 protein, Plasmodium falciparum
keywords: Plasmodium falciparum; RH5; blood-stage immunity; endemic population; malaria; prospective cohort study