Identification of Plasmodium falciparum Antigens by Antigenic Analysis of Genomic and Proteomic Data

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...

Full description

Saved in:
Bibliographic Details
Published inProceedings of the National Academy of Sciences - PNAS Vol. 100; no. 17; pp. 9952 - 9957
Main Authors Doolan, Denise L., Southwood, Scott, Freilich, Daniel A., Sidney, John, Graber, Norma L., Shatney, Lori, Bebris, Lolita, Florens, Laurence, Dobano, Carlota, Witney, Adam A., Appella, Ettore, Hoffman, Stephen L., Yates, John R., Carucci, Daniel J., Sette, Alessandro
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 19.08.2003
National Acad Sciences
Subjects
Adult
Algorithms
Alleles
Animals
Antigens
Antigens, Protozoan - genetics
Antigens, Protozoan - isolation & purification
Biological Sciences
Epitopes
Genes, Protozoan
Genome, Protozoan
Genomics
Humans
Immunization
In Vitro Techniques
Interferon-gamma - biosynthesis
Malaria Vaccines - genetics
Malaria Vaccines - immunology
Malaria Vaccines - isolation & purification
Male
Middle Aged
Molecular Sequence Data
Molecules
Open reading frames
Parasites
Plasmodium falciparum - genetics
Plasmodium falciparum - immunology
Proteases
Proteomics
Protozoan Proteins - genetics
Protozoan Proteins - immunology
Protozoan Proteins - isolation & purification
Reactivity
Sporozoites
T-Lymphocytes - immunology
Vaccination
Volunteerism
Online AccessGet full text

Cover

More Information
Summary: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.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ObjectType-Article-1
ObjectType-Feature-2
Present address: Unidad de Epidemiologia y Bioestadistica, Hospital Clinic, Universitat de Barcelona, Barcelona E-08036, Spain.
To whom correspondence should be addressed. E-mail: alex@liai.org.
Communicated by Howard M. Grey, La Jolla Institute for Allergy and Immunology, San Diego, CA, May 29, 2003
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).
Present address: La Jolla Institute for Allergy and Immunology, San Diego, CA 92121.
Present address: Department of Medical Microbiology, St. George's Hospital Medical School, London SW17 0RE, United Kingdom.
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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1633254100