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

Camila Tenorio França (1, 2) , Michael T White (1, 3) , Wen-Qiang He (2, 1) , Jessica B Hostetler (4, 5) , Jessica Brewster (1) , Gabriel Frato (6) , Indu Malhotra (6) , Jakub Gruszczyk (1) , Christele Huon (7) , Enmoore Lin (8) , Benson Kiniboro (8) , Anjali Yadava (9) , Peter Siba (8) , Mary R Galinski (10) , Julie Healer (2, 1) , Chetan Chitnis (7, 11) , Alan F Cowman (2, 1) , Eizo Takashima (9) , Takafumi Tsuboi (12) , Wai-Hong Tham (2, 1) , Rick M Fairhurst (5) , Julian C Rayner (4) , Christopher L King (6) , Ivo Mueller (1, 2, 7, 13)

1 WEHI - The Walter and Eliza Hall Institute of Medical Research
2 University of Melbourne
3 Imperial College London
4 The Wellcome Trust Sanger Institute [Cambridge]
5 Laboratory of Malaria and Vector Research [Rockville]
6 Case Western Reserve University [Cleveland]
7 Malaria : parasites et hôtes - Malaria : parasites and hosts
8 PNGIMR - Papua New Guinea Institute for Medical Research
9 Walter Reed Army Institute of Research
10 Emory University [Atlanta, GA]
11 ICGEB - International Centre for Genetic Engineering and Biotechnology [New Delhi]
12 Ehime University [Matsuyama, Japon]
13 ISGlobal - Instituto de Salud Global - Institute For Global Health [Barcelona]

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.

Keywords: IgG antibody; Plasmodium vivax; clinical malaria; epidemiology; global health; natural immunity; protection; vaccine

Domains: Life Sciences [q-bio]

Camila Tenorio França, Michael T White, Wen-Qiang He, Jessica B Hostetler, Jessica Brewster, et al.. Identification of highly-protective combinations of Plasmodium vivax recombinant proteins for vaccine development. eLife, 2017, 6, pp.e28673. ⟨10.7554/eLife.28673⟩. ⟨pasteur-03260305⟩