The abundance of genomic data from infectious microorganisms provides a wealth of information that may now be used to identify antigen targets for subunit vaccine development. Here we propose a strategy employing bioinformatics together with high throughput proteomics to rapidly identify target antigens from large and complex genomes, using Plasmodium falciparum as a model. Protective immunity to malaria can be induced by exposure to intact parasite. However, more than 5000 proteins are expressed during the life cycle of the Plasmodium spp. parasite, and the protein antigens mediating the protective immunity induced by whole organism vaccination are largely unknown. Only a small number of potential targets have been identified to date. Subunit vaccines currently in development are based on a single or few antigens and may therefore elicit too narrow a breadth of response, providing neither optimal protection nor protection on genetically diverse backgrounds. A high throughput protein _expression platform technology, called PCR Express, has been developed which can be used to rapidly generate the complete proteome from any sequenced microorganism. PCR Express allows thousands of different genes to be cloned, expressed and printed onto protein microarray chips, at a rate of more than 300 proteins per week. The chips can be used to scan serum from vaccinated or infected animals and humans and the immunodominant antigens identified. This valuable knowledge can then be immediately parlayed into additional areas of proposed research: 1) diagnostic tools for measuring malaria immunity in vaccinees; 2) development of simple, rapid, and sensitive immunological tools for assessing recent malaria exposure/ infection; 3) development of therapeutic anti-malaria neutralizing monoclonal human antibodies; 4) development of safe and effective candidate subunit malaria vaccines; and 5) accurate assessment of the quality of the immune responses elicited by alternative malaria vaccines. Of particular importance, there is a serious need for a malaria vaccine and the data generated from this application will be used to identify likely protective antigen candidates for a DNA or protein subunit vaccine against malaria.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43AI066791-01
Application #
6992937
Study Section
Special Emphasis Panel (ZRG1-IMM-G (12))
Program Officer
MO, Annie X Y
Project Start
2005-07-15
Project End
2007-06-30
Budget Start
2005-07-15
Budget End
2006-06-30
Support Year
1
Fiscal Year
2005
Total Cost
$298,279
Indirect Cost
Name
Immport Therapeutics, Inc.
Department
Type
DUNS #
159838106
City
Irvine
State
CA
Country
United States
Zip Code
92618
Chuquiyauri, Raul; Molina, Douglas M; Moss, Eli L et al. (2015) Genome-Scale Protein Microarray Comparison of Human Antibody Responses in Plasmodium vivax Relapse and Reinfection. Am J Trop Med Hyg 93:801-9
Skinner, Jeff; Huang, Chiung-Yu; Waisberg, Michael et al. (2015) Plasmodium falciparum Gametocyte-Specific Antibody Profiling Reveals Boosting through Natural Infection and Identifies Potential Markers of Gametocyte Exposure. Infect Immun 83:4229-36
Tan, Xiaolin; Traore, Boubacar; Kayentao, Kassoum et al. (2011) Hemoglobin S and C heterozygosity enhances neither the magnitude nor breadth of antibody responses to a diverse array of Plasmodium falciparum antigens. J Infect Dis 204:1750-61
Vigil, Adam; Chen, Chen; Jain, Aarti et al. (2011) Profiling the humoral immune response of acute and chronic Q fever by protein microarray. Mol Cell Proteomics 10:M110.006304
Barry, Alyssa E; Trieu, Angela; Fowkes, Freya J I et al. (2011) The stability and complexity of antibody responses to the major surface antigen of Plasmodium falciparum are associated with age in a malaria endemic area. Mol Cell Proteomics 10:M111.008326
Doolan, Denise L (2011) Plasmodium immunomics. Int J Parasitol 41:3-20
Nnedu, Obinna N; O'Leary, Michael P; Mutua, Daniel et al. (2011) Humoral immune responses to Plasmodium falciparum among HIV-1-infected Kenyan adults. Proteomics Clin Appl 5:613-23
Trieu, Angela; Kayala, Matthew A; Burk, Chad et al. (2011) Sterile protective immunity to malaria is associated with a panel of novel P. falciparum antigens. Mol Cell Proteomics 10:M111.007948
Crompton, Peter D; Kayala, Matthew A; Traore, Boubacar et al. (2010) A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray. Proc Natl Acad Sci U S A 107:6958-63