title: In vitro growth-inhibitory activity and malaria risk in a cohort study in mali.
abstract: Immunity to the asexual blood stage of Plasmodium falciparum is complex and likely involves several effector mechanisms. Antibodies are thought to play a critical role in malaria immunity, and a corresponding in vitro correlate of antibody-mediated immunity has long been sought to facilitate malaria vaccine development. The growth inhibition assay (GIA) measures the capacity of antibodies to limit red blood cell (RBC) invasion and/or growth of P. falciparum in vitro. In humans, naturally acquired and vaccine-induced P. falciparum-specific antibodies have growth-inhibitory activity, but it is unclear if growth-inhibitory activity correlates with protection from clinical disease. In a longitudinal study in Mali, purified IgGs, obtained from plasmas collected before the malaria season from 220 individuals aged 2 to 10 and 18 to 25 years, were assayed for growth-inhibitory activity. Malaria episodes were recorded by passive surveillance over the subsequent 6-month malaria season. Logistic regression showed that greater age (odds ratio [OR], 0.78; 95% confidence interval [95% CI], 0.63 to 0.95; P = 0.02) and growth-inhibitory activity (OR, 0.50; 95% CI, 0.30 to 0.85; P = 0.01) were significantly associated with decreased malaria risk in children. A growth-inhibitory activity level of 40% was determined to be the optimal cutoff for discriminating malaria-immune and susceptible individuals in this cohort, with a sensitivity of 97.0%, but a low specificity of 24.3%, which limited the assay's ability to accurately predict protective immunity and to serve as an in vitro correlate of antibody-mediated immunity. These data suggest that antibodies which block merozoite invasion of RBC and/or inhibit the intra-RBC growth of the parasite contribute to but are not sufficient for the acquisition of malaria immunity.
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, 12441 Parklawn Drive, Twinbrook 2 Bldg., Room 200F, Rockville, MD 20832, USA. pcrompton@niaid.nih.gov
authors.forename: Peter D
authors.initials: PD
authors.lastname: Crompton
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Miura
authors.forename: Boubacar
authors.initials: B
authors.lastname: Traore
authors.forename: Kassoum
authors.initials: K
authors.lastname: Kayentao
authors.forename: Aissata
authors.initials: A
authors.lastname: Ongoiba
authors.forename: Greta
authors.initials: G
authors.lastname: Weiss
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: Chiung-Yu
authors.initials: CY
authors.lastname: Huang
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.forename: Susan K
authors.initials: SK
authors.lastname: Pierce
mesh_terms: D000293:Adolescent; D000328:Adult; D000913:Antibodies, Protozoan / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006403:Hematologic Tests / Q000379:methods; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D066298:In Vitro Techniques; D008288:Malaria / Q000276:immunology*; D008297:Male; D008302:Mali; D010965:Plasmodium malariae / Q000276:immunology; D012306:Risk; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D007074:Immunoglobulin G