Identification of highly-protective combinations of Plasmodium vivax recombinant proteins for vaccine development

• Type of Material: Article
• Authors: Camila Tenorio Franca, Walter and Eliza Hall Institute; Michael T. White, Walter and Eliza Hall Institute; Wen-Qiang He, University of Melbourne; Jessica B. Hostetler, Wellcome Trust Sanger Institute; Jessica Brewster, Walter and Eliza Hall Institute; Gabriel Frato, Case Western Reserve University; Indu Malhotra, Case Western Reserve University; Jakub Gruszczyk, Walter and Eliza Hall Institute; Christele Huon, Institut Pasteur; Enmoore Lin, PNG Institute of Medical Research; Benson Kiniboro, PNG Institute of Medical Research; Anjali Yadava, Walter Reed Army Institute of Research; Peter Siba, PNG Institute of Medical Research; Mary Galinski, Emory University; Julie Healer, University of Melbourne; Chetan Chitnis, Institut Pasteur; Alan F. Cowman, University of Melbourne; Eizo Takashima, Walter Reed Army Institute of Research; Takafumi Tsuboi, Ehime University; Wai-Hong Tham, University of Melbourne; Rick M. Fairhurst, National Institutes of Health; Julian C. Rayner, Wellcome Trust Sanger Institute; Christopher L. King, Case Western Reserve University; Ivo Mueller, Walter and Eliza Hall Institute
• Language: English
• Date: 2017-09-26
• Publisher: eLife Sciences Publications
• Publication Version: Final Published Version
• Copyright Statement: © 2017, França et al
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.7554/eLife.28673
• Title of Journal or Parent Work: eLife
• ISSN: 2050-084X
• Volume: 6
• Grant/Funding Information: Malaria Eradication Scientific Alliance to Ivo Mueller.; National Health and Medical Research Council 1092789 to Alan F Cowman.; Australian Research Council Australian Research Council Future Fellowship to Wai-Hong Tham.; Medical Research Council MR/L012170/1 to Julian C Rayner.; National Institutes of Health U19AI089686 to Ivo Mueller.; Japan Society for the Promotion of Science JP26253026 to Takafumi Tsuboi.; National Health and Medical Research Council 1021544 to Ivo Mueller.; This paper was supported by the following grants:; National Health and Medical Research Council Senior Research Fellowship 1043345 to Ivo Mueller.; Medical Research Council MR/J002283/1 to Julian C Rayner.; National Institute of Allergy and Infectious Diseases Intramural Research Program to Rick M Fairhurst.; National Health and Medical Research Council Program Grant 1092789 to Ivo Mueller, Alan F Cowman.; National Institutes of Health AI063135 to Rick M Fairhurst.; University of Melbourne Melbourne International Postgraduate Scholarship to Camila Tenorio França, Wen-Qiang He.; National Health and Medical Research Council Independent Research Institute Infrastructure Support Scheme to Ivo Mueller.; Japan Society for the Promotion of Science JP15H05276 to Takafumi Tsuboi.; Japan Society for the Promotion of Science JP16K15266 to Takafumi Tsuboi.; Wellcome 098051 to Julian C Rayner.
• Keywords: FUNCTIONAL ANTIBODIES; ANTIBODY-RESPONSES; DUFFY-BINDING-PROTEIN; ERYTHROCYTE INVASION; NEW-GUINEAN CHILDREN; BLOOD-STAGE MALARIA; FALCIPARUM-MALARIA; MEROZOITE ANTIGENS; Life Sciences & Biomedicine; HUMAN MALARIA PARASITE; Science & Technology; Life Sciences & Biomedicine - Other Topics; Biology; P. VIVAX
• Research Categories: Biology, Genetics; Health Sciences, Epidemiology; Health Sciences, Immunology

Abstract

The study of antigenic targets of naturally-acquired immunity is essential to identify and prioritize antigens for further functional characterization. We measured total IgG antibodies to 38 P. vivax antigens, investigating their relationship with prospective risk of malaria in a cohort of 1-3 years old Papua New Guinean children. Using simulated annealing algorithms, the potential protective efficacy of antibodies to multiple antigen-combinations, and the antibody thresholds associated with protection were investigated for the first time. High antibody levels to multiple known and newly identified proteins were strongly associated with protection (IRR 0.44-0.74, p<0.001-0.041). Among five-antigen combinations with the strongest protective effect (>90%), EBP, DBPII, RBP1a, CyRPA, and PVX_081550 were most frequently identified; several of them requiring very low antibody levels to show a protective association. These data identify individual antigens that should be prioritized for further functional testing and establish a clear path to testing a multicomponent P. vivax vaccine.