rabies virus nucleoprotein as a carrier for新.pdf

Rabies virus nucleoprotein as a carrier for foreign antigens † † † † Martin L. Koser*, James P. McGettigan*, Gene S. Tan , Mary Ellen Smith , Hilary Koprowski , Bernhard Dietzschold , and Matthias J. Schnell*‡ Departments of *Biochemistry and Molecular Pharmacology and †Microbiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107-5541 Contributed by Hilary Koprowski, May 18, 2004 Rabies virus (RV) nucleoprotein (N) tightly encapsidates the Part of the immune protection from pathogens requires at genomic and antigenomic RNA of RV to form the viral ribonucle- least a strong B cell-mediated humoral response. It has been oprotein (RNP) complex. Antigens, such as N, presented in a highly previously shown with different virus-based expression systems organized structure are sufficient and even desirable to activate B that a variety of viral particles or virus-like particles can serve as cells to proliferate and produce antibodies. In addition to activat- carriers of foreign B cell epitopes within the viral capsid or ing B cells to proliferate, it has been shown that RV N in the RNP envelope protein of the viral particle. These epitope carriers complex induces potent T helper cell responses resulting in long- resulted in strong B cell responses against the expressed foreign lasting and strong humoral immune responses against RV. The epitopes indicating a usefulness of carrier proteins (14–20). possibility to systematically incorporate foreign genes into the However, most of these approaches are restricted to incorpora- genome of RV and produce a recombinant virus allows us to tion