eLife (Sep 2017)
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
Affiliations
- Camila Tenorio França
- ORCiD
- Division of Population Health and Immunity, Walter and Eliza Hall Institute, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
- Michael T White
- Division of Population Health and Immunity, Walter and Eliza Hall Institute, Parkville, Australia; MRC Center for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom
- Wen-Qiang He
- Department of Medical Biology, University of Melbourne, Parkville, Australia; Division of Infection and Immunity, Walter and Eliza Hall Institute, Parkville, Australia
- Jessica B Hostetler
- Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, United Kingdom; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States
- Jessica Brewster
- Division of Infection and Immunity, Walter and Eliza Hall Institute, Parkville, Australia
- Gabriel Frato
- Center for Global Health and Diseases, Case Western Reserve University, Cleveland, United States
- Indu Malhotra
- Center for Global Health and Diseases, Case Western Reserve University, Cleveland, United States
- Jakub Gruszczyk
- ORCiD
- Division of Infection and Immunity, Walter and Eliza Hall Institute, Parkville, Australia
- Christele Huon
- Malaria Parasite Biology and Vaccines Unit, Institut Pasteur, Paris, France
- Enmoore Lin
- Malaria Immuno-Epidemiology Unit, PNG Institute of Medical Research, Yagaum, Papua New Guinea
- Benson Kiniboro
- Malaria Immuno-Epidemiology Unit, PNG Institute of Medical Research, Yagaum, Papua New Guinea
- Anjali Yadava
- ORCiD
- Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, United States
- Peter Siba
- Malaria Immuno-Epidemiology Unit, PNG Institute of Medical Research, Yagaum, Papua New Guinea
- Mary R Galinski
- International Center for Malaria Research, Education, and Development, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, United States; Infectious Diseases Division, Department of Medicine, Emory University, Atlanta, United States
- Julie Healer
- Department of Medical Biology, University of Melbourne, Parkville, Australia; Division of Infection and Immunity, Walter and Eliza Hall Institute, Parkville, Australia
- Chetan Chitnis
- Malaria Parasite Biology and Vaccines Unit, Institut Pasteur, Paris, France; International Centre for Genetic Engineering and Biotechnology, New Delhi, India
- Alan F Cowman
- ORCiD
- Department of Medical Biology, University of Melbourne, Parkville, Australia; Division of Infection and Immunity, Walter and Eliza Hall Institute, Parkville, Australia
- Eizo Takashima
- Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, United States
- Takafumi Tsuboi
- Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Japan
- Wai-Hong Tham
- Department of Medical Biology, University of Melbourne, Parkville, Australia; Division of Infection and Immunity, Walter and Eliza Hall Institute, Parkville, Australia
- Rick M Fairhurst
- Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States
- Julian C Rayner
- Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
- Christopher L King
- Center for Global Health and Diseases, Case Western Reserve University, Cleveland, United States
- Ivo Mueller
- ORCiD
- Division of Population Health and Immunity, Walter and Eliza Hall Institute, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia; Malaria Parasites and Hosts Unit, Department of Parasites and Insect Vectors, Institut Pasteur, Paris, France; Barcelona Institute of Global Health, Barcelona, Spain
- DOI
- https://doi.org/10.7554/eLife.28673
- Journal volume & issue
-
Vol. 6
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.
Keywords
