Identification of highly-protective combinations of Plasmodium vivax recombinant proteins for vaccine development-Reference-Cited by-同舟云学术

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

Published:2017-09-26 Issue: Volume:6 Page:
ISSN:2050-084X
Container-title:eLife
language:en
Short-container-title:

Author:

França Camila Tenorio¹²^ORCID,White Michael T¹³,He Wen-Qiang²⁴,Hostetler Jessica B⁵⁶,Brewster Jessica⁴,Frato Gabriel⁷,Malhotra Indu⁷,Gruszczyk Jakub⁴^ORCID,Huon Christele⁸,Lin Enmoore⁹,Kiniboro Benson⁹,Yadava Anjali¹⁰^ORCID,Siba Peter⁹,Galinski Mary R¹¹¹²,Healer Julie²⁴,Chitnis Chetan⁸¹³,Cowman Alan F²⁴^ORCID,Takashima Eizo¹⁰,Tsuboi Takafumi¹⁴,Tham Wai-Hong²⁴,Fairhurst Rick M⁶,Rayner Julian C⁵,King Christopher L⁷,Mueller Ivo¹²¹⁵¹⁶^ORCID

Affiliation:

1. Division of Population Health and Immunity, Walter and Eliza Hall Institute, Parkville, Australia

2. Department of Medical Biology, University of Melbourne, Parkville, Australia

3. MRC Center for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom

4. Division of Infection and Immunity, Walter and Eliza Hall Institute, Parkville, Australia

5. Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, United Kingdom

6. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States

7. Center for Global Health and Diseases, Case Western Reserve University, Cleveland, United States

8. Malaria Parasite Biology and Vaccines Unit, Institut Pasteur, Paris, France

9. Malaria Immuno-Epidemiology Unit, PNG Institute of Medical Research, Yagaum, Papua New Guinea

10. Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, United States

11. International Center for Malaria Research, Education, and Development, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, United States

12. Infectious Diseases Division, Department of Medicine, Emory University, Atlanta, United States

13. International Centre for Genetic Engineering and Biotechnology, New Delhi, India

14. Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Japan

15. Malaria Parasites and Hosts Unit, Department of Parasites and Insect Vectors, Institut Pasteur, Paris, France

16. Barcelona Institute of Global Health, Barcelona, Spain

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.

Funder

University of Melbourne

National Health and Medical Research Council

Japan Society for the Promotion of Science

Australian Research Council

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Wellcome

Medical Research Council

Malaria Eradication Scientific Alliance

Publisher

eLife Sciences Publications, Ltd