title: Rabies virus nucleoprotein as a carrier for foreign antigens.
abstract: Rabies virus (RV) nucleoprotein (N) tightly encapsidates the genomic and antigenomic RNA of RV to form the viral ribonucleoprotein (RNP) complex. Antigens, such as N, presented in a highly organized structure are sufficient and even desirable to activate B cells to proliferate and produce antibodies. In addition to activating B cells to proliferate, it has been shown that RV N in the RNP complex induces potent T helper cell responses resulting in long-lasting and strong humoral immune responses against RV. The possibility to systematically incorporate foreign genes into the genome of RV and produce a recombinant virus allows us to examine whether the immunogenicity of foreign antigens can be enhanced by incorporation into the RV RNP structure. To test this hypothesis we constructed a recombinant RV expressing a RV N-GFP fusion protein. The chimeric N-GFP fusion protein was efficiently expressed and incorporated into RV RNP and virions. Moreover, the recombinant RNP induces a strong humoral immune response against GFP in mice. In contrast, mice inoculated with GFP alone or a combination of wild-type RV RNPs and GFP did not trigger any GFP-specific humoral responses using the same immunization schedule. These data indicate the usefulness of RV-based vectors as killed vaccines against other infectious diseases.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107-5541, USA.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Koser
authors.forename: James P
authors.initials: JP
authors.lastname: McGettigan
authors.forename: Gene S
authors.initials: GS
authors.lastname: Tan
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Smith
authors.forename: Hilary
authors.initials: H
authors.lastname: Koprowski
authors.forename: Bernhard
authors.initials: B
authors.lastname: Dietzschold
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Schnell
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000502:physiology*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D017931:DNA Primers; D005260:Female; D017930:Genes, Reporter; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D011820:Rabies virus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D011995:Recombination, Genetic; D012261:Ribonucleoproteins / Q000502:physiology*; D014764:Viral Proteins / Q000502:physiology*
chemical_list: D000956:Antigens, Viral; D017931:DNA Primers; D011993:Recombinant Fusion Proteins; D012261:Ribonucleoproteins; D014764:Viral Proteins