Profiling humoral immune responses to P. falciparum infection with protein microarrays

Doolan, Denise L., Mu, Yunxiang, Unal, Berkay, Sundaresh, Suman, Hirst, Siddiqua, Valdez, Conrad, Randall, Arlo, Molina, Douglas, Liang, Xiaowu, Freilich, Daniel A., Oloo, J. Aggrey, Blair, Peter L., Aguiar, Joao C., Baldi, Pierre, Davies, D. Huw, and Felgner, Philip L. (2008) Profiling humoral immune responses to P. falciparum infection with protein microarrays. Proteomics, 8 (22). pp. 4680-4694.

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Abstract

A complete description of the serological response following exposure of humans to complex pathogens is lacking and approaches suitable for accomplishing this are limited. Here we report, using malaria as a model, a method which elucidates the profile of antibodies that develop after natural or experimental infection or after vaccination with attenuated organisms, and which identifies immunoreactive antigens of interest for vaccine development or other applications. Expression vectors encoding 250 Plasmodium falciparum (Pf) proteins were generated by PCR/recombination cloning; the proteins were individually expressed with >90% efficiency in Escherichia coli cell-free in vitro transcription and translation reactions, and printed directly without purification onto microarray slides. The protein microarrays were probed with human sera from one of four groups which differed in immune status: sterile immunity or no immunity against experimental challenge following vaccination with radiation-attenuated Pf sporozoites, partial immunity acquired by natural exposure, and no previous exposure to Pf. Overall, 72 highly reactive Pf antigens were identified. Proteomic features associated with immunoreactivity were identified. Importantly, antibody profiles were distinct for each donor group. Information obtained from such analyses will facilitate identifying antigens for vaccine development, dissecting the molecular basis of immunity, monitoring the outcome of whole-organism vaccine trials, and identifying immune correlates of protection.

Item ID: 42737
Item Type: Article (Refereed Research - C1)
Keywords: antigen identification; Plasmodium falciparum; protein chip; proteome microarray; vaccine
ISSN: 1615-9861
Funders: National Institute of Allergy and Infectious Disease (NIAID), United States Army Medical Research and Materiel Command (USAMRMC), Naval Medical Research Centre (NMRC), Pfizer Australia Senior Research Fellowship (PASRF), National Institutes of Health (NIH), National Science Foundation (NSF), Institute for Genomics and Bioinformatics (IGB) (at University of California, Irvine)
Projects and Grants: NIAID 1R43AIU066791-01, NIAID U01AI056464, NIAID U01AI061363, USAMRMC 6000.RAD1.F.A0309, NIH Biomedical Informatics Training Program Grant 5T15LM007743, NSF Grant MRI EIA-0321390
Date Deposited: 23 Mar 2016 23:38
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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