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Journal of Virology, April 2000, p. 3455-3463, Vol. 74, No. 8
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
CD4+ T-Cell-Mediated Antiviral
Protection of the Upper Respiratory Tract in BALB/c Mice following
Parenteral Immunization with a Recombinant Respiratory Syncytial
Virus G Protein Fragment
Hélène
Plotnicky-Gilquin,1,*
Alain
Robert,1
Laurent
Chevalet,1
Jean-Francois
Haeuw,1
Alain
Beck,1
Jean-Yves
Bonnefoy,1
Christian
Brandt,2
Claire-Anne
Siegrist,2
Thien Ngoc
Nguyen,1 and
Ultan F.
Power1
Centre d'Immunologie Pierre Fabre, 74 164 St. Julien en Genevois, France,1 and
World Health Organization Collaborating Center for Neonatal
Vaccinology, Departments of Pathology and Pediatrics, University of
Geneva, Switzerland2
Received 7 September 1999/Accepted 13 January 2000
We analyzed the protective mechanisms induced against respiratory
syncytial virus subgroup A (RSV-A) infection in the lower and upper
respiratory tracts (LRT and URT) of BALB/c mice after intraperitoneal
immunization with a recombinant fusion protein incorporating residues
130 to 230 of RSV-A G protein (BBG2Na). Mother-to-offspring antibody
(Ab) transfer and adoptive transfer of BBG2Na-primed B cells into SCID
mice demonstrated that Abs are important for LRT protection but have no
effect on URT infection. In contrast, RSV-A clearance in the URT was
achieved in a dose-dependent fashion after adoptive transfer of
BBG2Na-primed T cells, while it was abolished in BBG2Na-immunized mice
upon in vivo depletion of CD4+, but not CD8+, T
cells. Furthermore, the conserved RSV-A G protein cysteines and
residues 193 and 194, overlapping the recently identified T helper cell
epitope on the G protein (P. W. Tebbey et al., J. Exp. Med.
188:1967-1972, 1998), were found to be essential for URT but not LRT
protection. Taken together, these results demonstrate for the first
time that CD4+ T cells induced upon parenteral immunization
with an RSV G protein fragment play a critical role in URT protection
of normal mice against RSV infection.
*
Corresponding author. Mailing address: Centre
d'Immunologie Pierre Fabre, 5, Av. Napoléon III, 74 164 St.
Julien en Genevois, France. Phone: 33.4 50 35 35 45. Fax: 33.4 50 35 35 90. E-mail: helene.plotnicky{at}pierre.fabre.com.
Journal of Virology, April 2000, p. 3455-3463, Vol. 74, No. 8
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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