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 journalArticle

61 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)789-798
Number of pages10
JournalJournal of Infectious Diseases
Volume209
Issue number5
DOIs
StatePublished - Mar 2014
Externally publishedYes

Keywords

  • Plasmodium falciparum
  • RH5
  • blood-stage immunity
  • endemic population
  • malaria
  • prospective cohort study

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Tran, T. M., Ongoiba, A., Coursen, J., Crosnier, C., Diouf, A., Huang, C. Y., Li, S., Doumbo, S., Doumtabe, D., Kone, Y., Bathily, A., Dia, S., Niangaly, M., Dara, C., Sangala, J., Miller, L. H., Doumbo, O. K., Kayentao, K., Long, C. A., ... Crompton, P. D. (2014). Naturally acquired antibodies specific for plasmodium falciparum reticulocyte-binding protein homologue 5 inhibit parasite growth and predict protection from malaria. Journal of Infectious Diseases, 209(5), 789-798. https://doi.org/10.1093/infdis/jit553