Using functional proteomics to develop non-invasive vaccines: application of proteomics in biodefense and human infectious diseases

抄録

Our research emphasis is to develop noninvasive needle-free vaccines primarily based on the establishment of proteome profiles of various biological samples in our laboratory (J. Invest. Dermatol., 121: 51-64, 2003). Our platform is to develop epicutaneous and intranasal vaccines via adenoviral (DNA)-based and E. coil (protein)-based vectors. In this talk, we will take Bacillus anthracis as an example, highlight for you how we utilize proteomics to 1) reveal the mechanism of noninvasive vaccines and 2) find novel antigens from Bacillus anthracis. Furthermore, the core technique of noninvasive vaccines based on proteome profiles will be discussed. Theoretically, bioterrorists with bioengineering capabilities may expose a nation of people to anthrax spores producing toxins other than PA-LF-EF. We have identified and purified several germination-associated proteins from Bacillus anthracis by using proteomics. These proteins were differentially expressed from spore dormancy to germination. Eleven identified proteins have been characterized including one secreted protein (Immune inhibitor A), four potential membrane-associated proteins (Camelysin, Germination protease, Alanine racemase, and L-arabinose transporter), two molecular chaperones (HSP60 and cpn60), two energy-related proteins (ATP synthase and GPDH) and one novel anthrax specific protein. Our data demonstrated that Camelysin is a secretory toxin with cell selectivity. The noninvasive vaccines generated in our lab targeting Camelysin illustrated that Camelysin is an excellent antigen and provides protection from anthrax spore challenge. Needle-free epicutaneous or intranasal vaccinations are easily performed with minimal assistance from professional medical personnel during a bioterrorist attack or infectious disease epidemic. The ease of this technology is also beneficial for populations where medical personnel are lacking. Another purpose for introducing the noninvasive vaccine techniques in this talk is to seek diversified collaboration to develop skin patch vaccines targeting human infectious diseases such as Severe Acute Respiratory Syndrome (SARS).