Identification of Highly-Protective combinations of plasmodium vivax recombinant proteins for vaccine development

Camila Tenorio França; Michael T. White; Wen Qiang He; Jessica B. Hostetler; Jessica Brewster; Gabriel Frato; Indu Malhotra; Jakub Gruszczyk; Christele Huon; Enmoore Lin; Benson Kiniboro; Anjali Yadava; Peter Siba; Mary R. Galinski; Julie Healer; Chetan Chitnis; Alan F. Cowman; Eizo Takashima; Takafumi Tsuboi; Wai Hong Tham; Rick M. Fairhurst; Julian C. Rayner; Christopher L. King; Ivo Mueller

doi:10.7554/eLife.28673

Identification of Highly-Protective combinations of plasmodium vivax recombinant proteins for vaccine development

Camila Tenorio França, Michael T. White, Wen Qiang He, Jessica B. Hostetler, Jessica Brewster, Gabriel Frato, Indu Malhotra, Jakub Gruszczyk, Christele Huon, Enmoore Lin, Benson Kiniboro, Anjali Yadava, Peter Siba, Mary R. Galinski, Julie Healer, Chetan Chitnis, Alan F. Cowman, Eizo Takashima, Takafumi Tsuboi, Wai Hong ThamRick M. Fairhurst, Julian C. Rayner, Christopher L. King, Ivo Mueller^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

58 Citations (Scopus)

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.

Original language	English
Article number	e28673
Number of pages	22
Journal	eLife
Volume	6
DOIs	https://doi.org/10.7554/eLife.28673
Publication status	Published - 26 Sept 2017
Externally published	Yes

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França, C. T., White, M. T., He, W. Q., Hostetler, J. B., Brewster, J., Frato, G., Malhotra, I., Gruszczyk, J., Huon, C., Lin, E., Kiniboro, B., Yadava, A., Siba, P., Galinski, M. R., Healer, J., Chitnis, C., Cowman, A. F., Takashima, E., Tsuboi, T., ... Mueller, I. (2017). Identification of Highly-Protective combinations of plasmodium vivax recombinant proteins for vaccine development. eLife, 6, Article e28673. https://doi.org/10.7554/eLife.28673

@article{8529547ed5f64afda3d4d3db189c4fb5,

title = "Identification of Highly-Protective combinations of plasmodium vivax recombinant proteins for vaccine development",

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.",

author = "Fran{\c c}a, {Camila Tenorio} and White, {Michael T.} and He, {Wen Qiang} and Hostetler, {Jessica B.} and Jessica Brewster and Gabriel Frato and Indu Malhotra and Jakub Gruszczyk and Christele Huon and Enmoore Lin and Benson Kiniboro and Anjali Yadava and Peter Siba and Galinski, {Mary R.} and Julie Healer and Chetan Chitnis and Cowman, {Alan F.} and Eizo Takashima and Takafumi Tsuboi and Tham, {Wai Hong} and Fairhurst, {Rick M.} and Rayner, {Julian C.} and King, {Christopher L.} and Ivo Mueller",

note = "Publisher Copyright: {\textcopyright} Fran{\c c}a et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.",

year = "2017",

month = sep,

day = "26",

doi = "10.7554/eLife.28673",

language = "English",

volume = "6",

journal = "eLife",

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França, CT, White, MT, He, WQ, Hostetler, JB, Brewster, J, Frato, G, Malhotra, I, Gruszczyk, J, Huon, C, Lin, E, Kiniboro, B, Yadava, A, Siba, P, Galinski, MR, Healer, J, Chitnis, C, Cowman, AF, Takashima, E, Tsuboi, T, Tham, WH, Fairhurst, RM, Rayner, JC, King, CL & Mueller, I 2017, 'Identification of Highly-Protective combinations of plasmodium vivax recombinant proteins for vaccine development', eLife, vol. 6, e28673. https://doi.org/10.7554/eLife.28673

TY - JOUR

T1 - Identification of Highly-Protective combinations of plasmodium vivax recombinant proteins for vaccine development

AU - França, Camila Tenorio

AU - White, Michael T.

AU - He, Wen Qiang

AU - Hostetler, Jessica B.

AU - Brewster, Jessica

AU - Frato, Gabriel

AU - Malhotra, Indu

AU - Gruszczyk, Jakub

AU - Huon, Christele

AU - Lin, Enmoore

AU - Kiniboro, Benson

AU - Yadava, Anjali

AU - Siba, Peter

AU - Galinski, Mary R.

AU - Healer, Julie

AU - Chitnis, Chetan

AU - Cowman, Alan F.

AU - Takashima, Eizo

AU - Tsuboi, Takafumi

AU - Tham, Wai Hong

AU - Fairhurst, Rick M.

AU - Rayner, Julian C.

AU - King, Christopher L.

AU - Mueller, Ivo

N1 - Publisher Copyright: © França et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

PY - 2017/9/26

Y1 - 2017/9/26

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85032986035&partnerID=8YFLogxK

U2 - 10.7554/eLife.28673

DO - 10.7554/eLife.28673

M3 - Article

C2 - 28949293

AN - SCOPUS:85032986035

SN - 2050-084X

VL - 6

JO - eLife

JF - eLife

M1 - e28673

ER -

Identification of Highly-Protective combinations of plasmodium vivax recombinant proteins for vaccine development

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