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Journal of Virology, October 2002, p. 10203-10210, Vol. 76, No. 20
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.20.10203-10210.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Gamma Interferon-Dependent Protection of the Mouse Upper Respiratory Tract following Parenteral Immunization with a Respiratory Syncytial Virus G Protein Fragment

Helene Plotnicky-Gilquin,* Dominique Cyblat-Chanal, Jean-Pierre Aubry, Thierry Champion, Alain Beck, Thien Nguyen, Jean-Yves Bonnefoy, and Nathalie Corvaïa

Centre d'Immunologie Pierre Fabre, F74164 Saint-Julien-en-Genevois, France

Received 14 February 2002/ Accepted 8 July 2002

The protective mechanisms induced in the mouse upper respiratory tract (URT) after intraperitoneal immunization with G2Na, a recombinant respiratory syncytial virus (RSV) G protein fragment (amino acid residues 130 to 230), were investigated. This protection was recently shown to be mediated by CD4+ T cells and to be critically dependent on the cysteines and amino acids 193 and 194 (H. Plotnicky-Gilquin, A. Robert, L. Chevalet, J.-F. Haeuw, A. Beck, J.-Y. Bonnefoy, C. Brandt, C.-A. Siegrist, T. N. Nguyen, and U. F. Power, J. Virol. 74:3455-3463, 2000). On G2Na, we identified a domain (amino acid residues 182 to 198) responsible for the T-helper-cell activity. This region coincided with a peptide designed AICK (residues 184 to 198) which includes the previously identified murine and human T-helper-cell epitope on the native G protein (P. W. Tebbey, M. Hagen, and G. E. Hancock, J. Exp. Med. 188:1967-1972, 1998). Immunization with AICK, in alum or complete Freund's adjuvant, significantly reduced nasal RSV titers in normal BALB/c mice. However, although lung protection was induced, in contrast to the case with live RSV, neither AICK nor G2Na was able to prevent nasal infection in gamma interferon (IFN-{gamma})-knockout mice. Anti-IFN-{gamma} neutralizing antibodies partially inhibited URT protection after administration to G2Na-immunized BALB/c mice. Furthermore, while purified CD4+ T cells from BALB/c mice immunized with G2Na or AICK significantly reduced lung and nasal infection of naive recipient mice after adoptive transfer, the cells from IFN-{gamma}-knockout mice had no effect. Together, these results demonstrated for the first time that the T-helper-cell epitope of RSV G protein induces URT protection in mice after parenteral immunization through a Th1-type, IFN-{gamma}-dependent mechanism.

* Corresponding author. Mailing address: Centre d'Immunologie Pierre Fabre, 5 Ave. Napoléon III, F74164 Saint-Julien-en-Genevois, France. Phone: (33) 450-35-35-55. Fax: (33) 450-35-35-90. E-mail: helene.plotnicky.gilquin{at}pierre-fabre.com.

Journal of Virology, October 2002, p. 10203-10210, Vol. 76, No. 20
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.20.10203-10210.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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