Naturally acquired antibodies target the glutamate-rich protein on intact merozoites and predict protection against febrile malaria

TY - JOUR

T1 - Naturally acquired antibodies target the glutamate-rich protein on intact merozoites and predict protection against febrile malaria

AU - Kana, Ikhlaq Hussain

AU - Adu, Bright

AU - Tiendrebeogo, Régis Wendpayangde

AU - Singh, Susheel Kumar

AU - Dodoo, Daniel

AU - Theisen, Michael

PY - 2017/2/15

Y1 - 2017/2/15

N2 - Background.: Plasmodium species antigens accessible at the time of merozoite release are likely targets of biologically functional antibodies.Methods.: Immunoglobulin G (IgG) antibodies against intact merozoites were quantified in the plasma of Ghanaian children from a longitudinal cohort using a novel flow cytometry-based immunofluorescence assay. Functionality of these antibodies, as well as glutamate-rich protein (GLURP)-specific affinity-purified IgG from malaria hyperimmune Liberian adults, was assessed by the opsonic phagocytosis (OP) assay.Results.: Opsonic phagocytosis activity was strongly associated (hazard ratio [HR] = 0.46; 95% confidence interval [CI] = .30-.73; P = .0008) with protection against febrile malaria. Of the antimerozoite-specific antibodies, only IgG3 was significantly associated with both OP and protection (HR = 0.53; 95% CI = .34-.84; Pcorrected = .03) against febrile malaria. Similarly, GLURP-specific antibodies previously shown to be protective against febrile malaria in this same cohort were significantly associated with OP activity in this study. GLURP-specific antibodies recognized merozoites and also mediated OP activity.Conclusions.: These findings support previous studies that found OP of merozoites to be associated with protection against malaria and further shows IgG3 and GLURP antibodies are key in the OP mechanism, thus giving further impetus for the development of malaria vaccines targeting GLURP.

AB - Background.: Plasmodium species antigens accessible at the time of merozoite release are likely targets of biologically functional antibodies.Methods.: Immunoglobulin G (IgG) antibodies against intact merozoites were quantified in the plasma of Ghanaian children from a longitudinal cohort using a novel flow cytometry-based immunofluorescence assay. Functionality of these antibodies, as well as glutamate-rich protein (GLURP)-specific affinity-purified IgG from malaria hyperimmune Liberian adults, was assessed by the opsonic phagocytosis (OP) assay.Results.: Opsonic phagocytosis activity was strongly associated (hazard ratio [HR] = 0.46; 95% confidence interval [CI] = .30-.73; P = .0008) with protection against febrile malaria. Of the antimerozoite-specific antibodies, only IgG3 was significantly associated with both OP and protection (HR = 0.53; 95% CI = .34-.84; Pcorrected = .03) against febrile malaria. Similarly, GLURP-specific antibodies previously shown to be protective against febrile malaria in this same cohort were significantly associated with OP activity in this study. GLURP-specific antibodies recognized merozoites and also mediated OP activity.Conclusions.: These findings support previous studies that found OP of merozoites to be associated with protection against malaria and further shows IgG3 and GLURP antibodies are key in the OP mechanism, thus giving further impetus for the development of malaria vaccines targeting GLURP.

U2 - 10.1093/infdis/jiw617

DO - 10.1093/infdis/jiw617

M3 - Journal article

C2 - 28329101

SN - 0022-1899

VL - 215

SP - 623

EP - 630

JO - The Journal of Infectious Diseases

JF - The Journal of Infectious Diseases

IS - 4

ER -