Gamma interferon-dependent protection of the mouse upper respiratory tract following parenteral immunization with a respiratory syncytial virus G protein fragment.
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.
Plotnicky-Gilquin
Helene
H
Centre d'Immunologie Pierre Fabre, F74164 Saint-Julien-en-Genevois, France. helene.plotnicky.gilquin@pierre-fabre.com
Cyblat-Chanal
Dominique
D
Aubry
Jean-Pierre
JP
Champion
Thierry
T
Beck
Alain
A
Nguyen
Thien
T
Bonnefoy
Jean-Yves
JY
Corvaïa
Nathalie
N
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006801:Humans; D007112:Immunity, Maternally-Acquired / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D012137:Respiratory System / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D022261:Respiratory Syncytial Virus Vaccines; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D007371:Interferon-gamma