Ikhlaq Hussain Kana1,2,3, Bright Adu4, Régis Wendpayangde Tiendrebeogo1,2,3, Susheel Kumar Singh1,2,3, Daniel Dodoo4, Michael Theisen1,2,3. 1. Department for Congenital Disorders, Statens Serum Institute, Copenhagen, Denmark 2. Centre for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen. 3. Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark 4. Noguchi Memorial Institute for Medical Research, University of Ghana, Legon.
Abstract
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.
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.
Authors: Christian N Nguetse; Johnson Adeyemi Ojo; Charles Nchotebah; Moses Nkechukwu Ikegbunam; Christian G Meyer; Bolaji N Thomas; Thirumalaisamy P Velavan; Olusola Ojurongbe Journal: Am J Trop Med Hyg Date: 2018-01-18 Impact factor: 2.345
Authors: Sylvester Dassah; Bright Adu; Régis W Tiendrebeogo; Susheel K Singh; Fareed K N Arthur; Sodiomon B Sirima; Michael Theisen Journal: Front Immunol Date: 2022-06-02 Impact factor: 8.786
Authors: Celia Dechavanne; Sebastien Dechavanne; Ibrahim Sadissou; Adjimon Gatien Lokossou; Fernanda Alvarado; Magalie Dambrun; Kabirou Moutairou; David Courtin; Gregory Nuel; Andre Garcia; Florence Migot-Nabias; Christopher L King Journal: PLoS Med Date: 2017-10-09 Impact factor: 11.069