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 Miura; Gavin J Wright; Boubacar Traore; Peter D Crompton

doi:10.1093/infdis/jit553

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 journal › Article › peer-review

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.

Original language	English
Pages (from-to)	789-798
Number of pages	10
Journal	The Journal of Infectious Diseases
Volume	209
Issue number	5
Early online date	16 Oct 2013
DOIs	https://doi.org/10.1093/infdis/jit553
Publication status	Published - 1 Mar 2014

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10.1093/infdis/jit553

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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. The Journal of Infectious Diseases, 209(5), 789-798. https://doi.org/10.1093/infdis/jit553

@article{62a56141912c43f8b6cc31c2d860bd94,

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. CLINICAL TRIALS REGISTRATION: NCT01322581.",

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

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doi = "10.1093/infdis/jit553",

language = "English",

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Tran, TM, 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, LH, Doumbo, OK, Kayentao, K, Long, CA, Miura, K, Wright, GJ, Traore, B & Crompton, PD 2014, 'Naturally acquired antibodies specific for Plasmodium falciparum reticulocyte-binding protein homologue 5 inhibit parasite growth and predict protection from malaria.', The Journal of Infectious Diseases, vol. 209, no. 5, pp. 789-798. https://doi.org/10.1093/infdis/jit553

Naturally acquired antibodies specific for Plasmodium falciparum reticulocyte-binding protein homologue 5 inhibit parasite growth and predict protection from malaria. / Tran, Tuan M; Ongoiba, Aissata; Coursen, Jill et al.
In: The Journal of Infectious Diseases, Vol. 209, No. 5, 01.03.2014, p. 789-798.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Naturally acquired antibodies specific for Plasmodium falciparum reticulocyte-binding protein homologue 5 inhibit parasite growth and predict protection from malaria.

AU - Tran, Tuan M

AU - Ongoiba, Aissata

AU - Coursen, Jill

AU - Crosnier, Cecile

AU - Diouf, Ababacar

AU - Huang, Chiung-Yu

AU - Li, Shanping

AU - Doumbo, Safiatou

AU - Doumtabe, Didier

AU - Kone, Younoussou

AU - Bathily, Aboudramane

AU - Dia, Seydou

AU - Niangaly, Moussa

AU - Dara, Charles

AU - Sangala, Jules

AU - Miller, Louis H

AU - Doumbo, Ogobara K

AU - Kayentao, Kassoum

AU - Long, Carole A

AU - Miura, Kazutoyo

AU - Wright, Gavin J

AU - Traore, Boubacar

AU - Crompton, Peter D

PY - 2014/3/1

Y1 - 2014/3/1

N2 - 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.

AB - 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.

U2 - 10.1093/infdis/jit553

DO - 10.1093/infdis/jit553

M3 - Article

SN - 0022-1899

VL - 209

SP - 789

EP - 798

JO - The Journal of Infectious Diseases

JF - The Journal of Infectious Diseases

IS - 5

ER -