Lyssavirus glycoproteins expressing immunologically potent foreign B cell and cytotoxic T lymphocyte epitopes as prototypes for multivalent vaccines.
Truncated and chimeric lyssavirus glycoprotein (G) genes were used to carry and express non-lyssavirus B and T cell epitopes for DNA-based immunization of mice, with the aim of developing a multivalent vaccine prototype. Truncated G (GPVIII) was composed of the C-terminal half (aa 253-503) of the Pasteur rabies virus (PV: genotype 1) G containing antigenic site III and the transmembrane and cytoplasmic domains. The chimeric G (GEBL1-PV) was composed of the N-terminal half (aa 1-250) of the European bat lyssavirus 1 (genotype 5) G containing antigenic site II linked to GPVIII. Antigenic sites II and III are involved in the induction of virus-neutralizing antibodies. The B cell epitope was the C3 neutralization epitope of the poliovirus type 1 capsid VP1 protein. The T cell epitope was the H2d MHC I-restricted epitope of the nucleoprotein of lymphocytic choriomeningitis virus (LCMV) involved in the induction of both cytotoxic T cell (CTL) production and protection against LCMV. Truncated G carrying foreign epitopes induced weak antibody production against rabies and polio viruses and provided weak protection against LCMV. In contrast, the chimeric plasmid containing various combinations of B and CTL epitopes elicited simultaneous immunological responses against both parental lyssaviruses and poliovirus and provided good protection against LCMV. The level of humoral and cellular immune responses depended on the order of the foreign epitopes inserted. Our results demonstrate that chimeric lyssavirus glycoproteins can be used not only to broaden the spectrum of protection against lyssaviruses, but also to express foreign B and CTL epitopes. The potential usefulness of chimeric lyssavirus glycoproteins for the development of multivalent vaccines against animal diseases and zoonoses, including rabies, is discussed.
Desmézières
Emmanuel
E
Laboratoire des Lyssavirus1, Laboratoire de Virologie Expérimentale2 and Laboratoire d'Epidémiologie Moléculaire des Entérovirus3, Institut Pasteur 25, rue du Dr Roux, 75724 Paris Cedex 15, France.
Jacob
Yves
Y
Laboratoire des Lyssavirus1, Laboratoire de Virologie Expérimentale2 and Laboratoire d'Epidémiologie Moléculaire des Entérovirus3, Institut Pasteur 25, rue du Dr Roux, 75724 Paris Cedex 15, France.
Saron
Marie-Françoise
MF
Laboratoire des Lyssavirus1, Laboratoire de Virologie Expérimentale2 and Laboratoire d'Epidémiologie Moléculaire des Entérovirus3, Institut Pasteur 25, rue du Dr Roux, 75724 Paris Cedex 15, France.
Delpeyroux
Francis
F
Laboratoire des Lyssavirus1, Laboratoire de Virologie Expérimentale2 and Laboratoire d'Epidémiologie Moléculaire des Entérovirus3, Institut Pasteur 25, rue du Dr Roux, 75724 Paris Cedex 15, France.
Tordo
Noël
N
Laboratoire des Lyssavirus1, Laboratoire de Virologie Expérimentale2 and Laboratoire d'Epidémiologie Moléculaire des Entérovirus3, Institut Pasteur 25, rue du Dr Roux, 75724 Paris Cedex 15, France.
Perrin
Pierre
P
Laboratoire des Lyssavirus1, Laboratoire de Virologie Expérimentale2 and Laboratoire d'Epidémiologie Moléculaire des Entérovirus3, Institut Pasteur 25, rue du Dr Roux, 75724 Paris Cedex 15, France.
D000595:Amino Acid Sequence; D000818:Animals; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D005260:Female; D018114:Lyssavirus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014765:Viral Vaccines