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). pp. 1-15.

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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.

Item ID: 41448
Item Type: Article (Research - C1)
ISSN: 1535-9484
Funders: National Health and Medical Research Council of Australia (NHMRC), National Institute of Allergy and Infectious Diseases (NIAID), National Naval Medical Centre (NNMC), Pfizer
Projects and Grants: NHMRC grant No. 496600, NIAID grant R43AI066791, NNMC 62787A.870.F.1432
Date Deposited: 11 Feb 2016 03:55
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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