Global control of infectious diseases depends upon the ability to treat individuals in developing countries with vaccines and therapeutics. Many developing countries lack the economic resources to purchase modern medical therapeutics such as vaccines and antiviral drugs, and there is a growing need for inexpensive, easily produced and delivered sources of vaccines and antiviral reagents. Plant virus particles provide an excellent means to combat this problem. Plant viruses are inexpensive, stable, and easy to produce in large quantities. For instance, cowpea mosaic virus (CPMV) has been particularly well characterized genetically, biochemically and structurally. CPMV can be engineered to display foreign immunogenic or antiviral peptide sequences on the virus particle surface. Each chimeric CPMV particle displays 60 copies of the relevant protein epitope and the particles themselves are heat and acid-stable.
In Specific Aims I -III, in vivo animal models will be combined with structural and biochemical studies to explore novel vaccine and antiviral applications of the CPMV chimera technology. First, a conformational antibody epitope will be displayed on the surface of CPMV and its immunogenicity in vivo will be determined. Second, cytotoxic T lymphocyte (CTL) epitopes designed to elicit cellular antiviral immunity will be displayed on the surface of CPMV. The ability of the CPMV-CTL epitope chimeras to induce antiviral CTL will tested in vivo. Third, a peptide sequence having antiviral activity in vitro will be presented on CPMV and the antiviral activity of the resulting chimera assessed in vivo. In the fourth Specific Aim, experiments to further define the biophysical and structural rules for design and presentation of complex multimeric structures and conformational epitopes on CPMV will be carried out. Together these studies will expand the uses of the CPMV chimera technology to include novel and important vaccine and antiviral approaches. These principles can be applied to the development of affordable CPMV-based vaccine and therapeutic reagents for bacterial, fungal, and parasitic infectious disease as well.
| Lewis, John D; Destito, Giuseppe; Zijlstra, Andries et al. (2006) Viral nanoparticles as tools for intravital vascular imaging. Nat Med 12:354-60 |
| Rae, Chris S; Khor, Ing Wei; Wang, Qian et al. (2005) Systemic trafficking of plant virus nanoparticles in mice via the oral route. Virology 343:224-35 |
| Manchester, M; Rall, G F (2001) Model Systems: transgenic mouse models for measles pathogenesis. Trends Microbiol 9:19-23 |
