Abstract

We plan to develop the novel vaccines targeting the released proteins/peptides (secretome) during the early infection of Bacillus anthracis. In the past years, we had established the proteomic techniques to identify novel anthrax antigens. Several vector-based vaccines encoding these novel anthrax antigens have been constructed in our laboratory. In addition, we have published a proteome of Bacillus anthracis by identifying spore proteins associated with germination and early outgrowth. However, the released proteins/peptides (secretome) of Bacillus anthracis are not included in our and other published anthrax proteomes. In this proposal, we will mainly employ the mass spectrometric techniques to identify the anthrax secretomes with/without protein separation by 2-D electrophoresis. We will collect the secretomes from anthrax-infected mice using capillary ultrafiltration (CDF) probes in order to capture the in vivo low abundant and secretory proteins/peptides. The CDF probes are a novel technique recently developed in our laboratory to collect low abundant and secretory proteins from mice. We plan to emphasize on the proteins/peptides released during the early stages of anthrax infection. Our hypothesis is that vaccines targeting the early stages of anthrax infection (upstream events) will block the downstream events including the production of protective antigen (PA), lethal factor (LF), and edema factor (EF). In order to construct more effective vaccines, we will determine the cytotoxicities and immunogenicities of anthrax secretomes. In parallel, we will evaluate the efficacies of vaccines which encoded secretomes of early anthrax infection as compared to current PA/LF-based vaccines. Lastly, we have identified a novel toxin called camelysin-like protein (CLP) which exerts immunogenic and is released from dormant spores during the early stage of the anthrax life cycle. This protein will thus serve as a positive control to evaluate novel antigens identified in the proposed studies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
7R01AI067395-06
Application #
8068586
Study Section
Special Emphasis Panel (ZRG1-IHD (01))
Program Officer
Breen, Joseph J
Project Start
2006-03-01
Project End
2011-06-30
Budget Start
2010-03-01
Budget End
2010-06-30
Support Year
6
Fiscal Year
2009
Total Cost
$25,089
Indirect Cost

  Institution

Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Chen, Hui-Wen; Liu, Pei-Feng; Liu, Yu-Tsueng et al. (2016) Nasal commensal Staphylococcus epidermidis counteracts influenza virus. Sci Rep 6:27870
Liu, Pei-Feng; Hsieh, Yao-Dung; Lin, Ya-Ching et al. (2015) Propionibacterium acnes in the pathogenesis and immunotherapy of acne vulgaris. Curr Drug Metab 16:245-54
Liu, Pei-Feng; Cheng, Jin-Shiung; Sy, Cheng-Len et al. (2015) IsaB Inhibits Autophagic Flux to Promote Host Transmission of Methicillin-Resistant Staphylococcus aureus. J Invest Dermatol 135:2714-2722
Liu, P-F; Huang, I-F; Shu, C-W et al. (2013) Halitosis vaccines targeting FomA, a biofilm-bridging protein of fusobacteria nucleatum. Curr Mol Med 13:1358-67
Wang, Yanhan; Zhu, Wenhong; Shu, Muya et al. (2012) The response of human skin commensal bacteria as a reflection of UV radiation: UV-B decreases porphyrin production. PLoS One 7:e47798
Zhu, Wenhong; Gallo, Richard L; Huang, Chun-Ming (2012) Sampling human indigenous saliva peptidome using a lollipop-like ultrafiltration probe: simplify and enhance peptide detection for clinical mass spectrometry. J Vis Exp :e4108
Chen, Chao-Hsuan; Wang, Yanhan; Nakatsuji, Teruaki et al. (2011) An innate bactericidal oleic acid effective against skin infection of methicillin-resistant Staphylococcus aureus: a therapy concordant with evolutionary medicine. J Microbiol Biotechnol 21:391-9
Lo, Chih-Wei; Lai, Yiu-Kay; Liu, Yu-Tsueng et al. (2011) Staphylococcus aureus hijacks a skin commensal to intensify its virulence: immunization targeting ?-hemolysin and CAMP factor. J Invest Dermatol 131:401-9
Liu, Pei-Feng; Nakatsuji, Teruaki; Zhu, Wenhong et al. (2011) Passive immunoprotection targeting a secreted CAMP factor of Propionibacterium acnes as a novel immunotherapeutic for acne vulgaris. Vaccine 29:3230-8
Nakatsuji, Teruaki; Tang, De-chu C; Zhang, Liangfang et al. (2011) Propionibacterium acnes CAMP factor and host acid sphingomyelinase contribute to bacterial virulence: potential targets for inflammatory acne treatment. PLoS One 6:e14797

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