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Journal of Virology, January 1999, p. 225-233, Vol. 73, No. 1
Laboratoire des Lyssavirus, Institut Pasteur,
75724 Paris Cedex 15, France
Received 13 August 1998/Accepted 12 October 1998
The rabies virus glycoprotein molecule (G) can be divided into two
parts separated by a flexible hinge: the NH2 half (site II
part) containing antigenic site II up to the linear region (amino acids
[aa] 253 to 275 encompassing epitope VI [aa 264]) and the COOH half
(site III part) containing antigenic site III and the transmembrane and
cytoplasmic domains. The structural and immunological roles of each
part were investigated by cell transfection and mouse DNA-based
immunization with homogeneous and chimeric G genes formed by fusion of
the site II part of one genotype (GT) with the site III part of the
same or another GT. Various site II-site III combinations between G
genes of PV (Pasteur virus strain) rabies (GT1), Mokola (GT3), and EBL1
(European bat lyssavirus 1 [GT5]) viruses were tested. Plasmids
pGPV-PV, pGMok-Mok, pGMok-PV, and pGEBL1-PV induced transient
expression of correctly transported and folded antigens in
neuroblastoma cells and virus-neutralizing antibodies against parental
viruses in mice, whereas, pG-PVIII (site III part only) and pGPV-Mok
did not. The site III part of PV (GT1) was a strong inducer of T helper
cells and was very effective at presenting the site II part of various
GTs. Both parts are required for correct folding and transport of
chimeric G proteins which have a strong potential value for
immunological studies and development of multivalent vaccines. Chimeric
plasmid pGEBL1-PV broadens the spectrum of protection against European
lyssavirus genotypes (GT1, GT5, and GT6).
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Chimeric Lyssavirus Glycoproteins with Increased
Immunological Potential
*
Corresponding author. Mailing address: Laboratoire des
Lyssavirus, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris Cedex 15, France. Phone: (33) 1 45 68 87 56. Fax: (33) 1 40 61 32 56. E-mail:pperrin{at}pasteur.fr.
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