Sterile protective immunity to malaria is associated with a panel of novel P. falciparum antigens

Trieu, Angela, Kayala, Matthew A., Burk, Chad, Molina, Douglas M., Freilich, Daniel A., Richie, Thomas L., Baldi, Pierre, Felgner, Philip L. and Doolan, Denise L. (2011) Sterile protective immunity to malaria is associated with a panel of novel P. falciparum antigens. Molecular and Cellular Proteomics, 10 9: 1-15. doi:10.1074/mcp.M111.007948


Author Trieu, Angela
Kayala, Matthew A.
Burk, Chad
Molina, Douglas M.
Freilich, Daniel A.
Richie, Thomas L.
Baldi, Pierre
Felgner, Philip L.
Doolan, Denise L.
Title Sterile protective immunity to malaria is associated with a panel of novel P. falciparum antigens
Formatted title
Sterile protective immunity to malaria is associated with a panel of novel P. falciparum antigens
Journal name Molecular and Cellular Proteomics   Check publisher's open access policy
ISSN 1535-9476
1535-9484
Publication date 2011-09
Sub-type Article (original research)
DOI 10.1074/mcp.M111.007948
Volume 10
Issue 9
Start page 1
End page 15
Total pages 15
Place of publication Bethesda, MD, United States
Publisher American Society for Biochemistry and Molecular Biology
Collection year 2012
Language eng
Formatted abstract
The development of an effective malaria vaccine remains a global public health priority. Less than 0.5% of the Plasmodium falciparum genome has been assessed as potential vaccine targets and candidate vaccines have been based almost exclusively on single antigens. It is possible that the failure to develop a malaria vaccine despite decades of effort might be attributed to this historic focus. To advance malaria vaccine development, we have fabricated protein microarrays representing 23% of the entire P. falciparum proteome and have probed these arrays with plasma from subjects with sterile protection or no protection after experimental immunization with radiation attenuated P. falciparum sporozoites. A panel of 19 pre-erythrocytic stage antigens was identified as strongly associated with sporozoite-induced protective immunity; 16 of these antigens were novel and 85% have been independently identified in sporozoite and/or liver stage proteomic or transcriptomic data sets. Reactivity to any individual antigen did not correlate with protection but there was a highly significant difference in the cumulative signal intensity between protected and not protected individuals. Functional annotation indicates that most of these signature proteins are involved in cell cycle/DNA processing and protein synthesis. In addition, 21 novel blood-stage specific antigens were identified. Our data provide the first evidence that sterile protective immunity against malaria is directed against a panel of novel P. falciparum antigens rather than one antigen in isolation. These results have important implications for vaccine development, suggesting that an efficacious malaria vaccine should be multivalent and targeted at a select panel of key antigens, many of which have not been previously characterized.
Keyword Cd8+ T-cells
Apical Membrane Antigen-1
Plasmodium-falciparum
Circumsporozoite protein
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
 
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