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

• 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
• Journal Title: eLife
• Volume: Volume 6
• Publisher: eLife Sciences Publications | 2017-09-26
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.7554/eLife.28673
• Subjects: Health Sciences, Immunology; Health Sciences, Epidemiology; Biology, Genetics
• Keywords: Science & Technology; Life Sciences & Biomedicine; Biology; Life Sciences & Biomedicine - Other Topics; NEW-GUINEAN CHILDREN; DUFFY-BINDING-PROTEIN; HUMAN MALARIA PARASITE; BLOOD-STAGE MALARIA; FALCIPARUM-MALARIA; ANTIBODY-RESPONSES; P. VIVAX; MEROZOITE ANTIGENS; FUNCTIONAL ANTIBODIES; ERYTHROCYTE INVASION

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.