An Antibody Screen of a Plasmodium vivax Antigen Library Identifies Novel Merozoite Proteins Associated with Clinical Protection
Year: 2016
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Elimination of Plasmodium vivax malaria would be greatly facilitated by the development of an effective vaccine. A comprehensive and systematic characterization of antibodies to P. vivax antigens in exposed populations is useful in guiding rational vaccine design. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated antibodies to a large library of P. vivax entire ectodomain merozoite proteins in 2 Asia-Pacific populations, analysing the relationship of antibody levels with markers of current and cumulative malaria exposure, and socioeconomic and clinical indicators. 29 antigenic targets of natural immunity were identified. Of these, 12 highly-immunogenic proteins were strongly associated with age and thus cumulative lifetime exposure in Solomon Islanders (P<0.001-0.027). A subset of 6 proteins, selected on the basis of immunogenicity and expression levels, were used to examine antibody levels in plasma samples from a population of young Papua New Guinean children with well-characterized individual differences in exposure. This analysis identified a strong association between reduced risk of clinical disease and antibody levels to P12, P41, and a novel hypothetical protein that has not previously been studied, PVX_081550 (IRR 0.46-0.74; P<0.001-0.041). CONCLUSION/SIGNIFICANCE: These data emphasize the benefits of an unbiased screening approach in identifying novel vaccine candidate antigens. Functional studies are now required to establish whether PVX_081550 is a key component of the naturally-acquired protective immune response, a biomarker of immune status, or both.
Source: PLoS neglected tropical diseases
Institutions: The University of Melbourne, Walter and Eliza Hall Institute of Medical Research, National Institutes of Health, Wellcome Sanger Institute, National Institute of Allergy and Infectious Diseases, Imperial College London, Papua New Guinea Institute of Medical Research, Case Western Reserve University, Barcelona Institute for Global Health, Universitat de Barcelona
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,670
Funders: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Wellcome Trust, Australian Government, University of Melbourne, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, National Institute of Allergy and Infectious Diseases
Awards: Research to control and eliminate malaria in SE Asia and SW Pacific, Identifying Bottlenecks to Malaria Transmission in Papua New Guinea, Senior Research Fellowship, G1924830673, G4839860845, G5383059120, The effect of mixed Plasmodium infections on morbidity, G6752123328, G7750268118, G8152839422, Wellcome Trust Sanger Institute - generic account for deposition of all core- funded research papers, A comprehensive survey of protein-protein interactions between Plasmodium falciparum merozoites and human receptors
OpenAlex ID: W2396788880