Identification of Plasmodium falciparum antigens by antigenic analysis of genomic and proteomic data

doi:10.1073/pnas.1633254100

Identification of Plasmodium falciparum antigens by antigenic analysis of genomic and proteomic data

^aMalaria Program, Naval Medical Research Center, Silver Spring, MD 20910-7500; ^bDepartment of Molecular Microbiology and Immunology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205-2179; ^cEpimmune, Inc., San Diego, CA 92121; ^eHenry M. Jackson Foundation, Rockville, MD 20852; ^fThe Scripps Research Institute, La Jolla, CA 92037; ^kTorrey Mesa Research Institute, San Diego, CA 92121; and ⁱLaboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892

Communicated by Howard M. Grey, La Jolla Institute for Allergy and Immunology, San Diego, CA, May 29, 2003 (received for review March 7, 2003)

Abstract

The recent explosion in genomic sequencing has made available a wealth of data that can now be analyzed to identify protein antigens, potential targets for vaccine development. Here we present, in the context of Plasmodium falciparum, a strategy that rapidly identifies target antigens from large and complex genomes. Sixteen antigenic proteins recognized by volunteers immunized with radiation-attenuated P. falciparum sporozoites, but not by mock immunized controls, were identified. Several of these were more antigenic than previously identified and well characterized P. falciparum-derived protein antigens. The data suggest that immune responses to Plasmodium are dispersed on a relatively large number of parasite antigens. These studies have implications for our understanding of immunodominance and breadth of responses to complex pathogens.

Footnotes

↵ l To whom correspondence should be addressed. E-mail: alex{at}liai.org.
↵ d Present address: La Jolla Institute for Allergy and Immunology, San Diego, CA 92121.
↵ g Present address: Unidad de Epidemiologia y Bioestadistica, Hospital Clinic, Universitat de Barcelona, Barcelona E-08036, Spain.
↵ h Present address: Department of Medical Microbiology, St. George's Hospital Medical School, London SW17 0RE, United Kingdom.
↵ j Present address: Sanaria, Gaithersburg, MD 20878.
Abbreviations: PBMC, peripheral blood mononuclear cells; ELISPOT, enzyme-linked immunospot; CSP, circumsporozoite protein; EXP-1, exported protein 1; LSA-1, liver-stage antigen 1; MIC, measured IC₅₀ nM value; MudPIT, multidimensional protein identification technology; SFC, spot-forming cells; SSP2, sporozoite surface protein 2; PIC, predicted IC₅₀ nM value.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. PF10_0179, PFL0800c, PFI0165c, PFC0210c, PF14_0372, PF11_0341, mal4T2c4.p1t1, PF13_0278, PFE0765w, PF11_0479, PFC0450w, PF14_0074, PFC0700c, PF14_0291, MAL8P1.78, MAL13P1.218, PFD0425w, PF13_0320, PF11_0435, PFI0260, PF11_0226, PFA0515w, MAL6P1.252, PF14_0236, PF14_0751, PF14_0648, and PF11_0456).