TY - JOUR
T1 - Mucosal delivery of a respiratory syncytial virus CTL peptide with enterotoxin-based adjuvants elicits protective, immunopathogenic, and immunoregulatory antiviral CD8+ T cell responses
AU - Simmons, C. P.
AU - Hussell, T.
AU - Sparer, T.
AU - Walzl, G.
AU - Openshaw, P.
AU - Dougan, G.
PY - 2001/1/15
Y1 - 2001/1/15
N2 - In an effort to develop a safe and effective vaccine against respiratory syncytial virus (RSV), we used Escherichia coli heat-labile toxin (LT), and LTK63 (an LT mutant devoid of ADP-ribosyltransferase activity) to elicit murine CD8+ CTL responses to an intranasally codelivered CTL peptide from the second matrix protein (M2) of RSV. M282-90-specific CD8+ T cells were detected by IFN-γ enzyme-linked immunospot and 51Cr release assay in local and systemic lymph nodes, and their induction was dependent on the use of a mucosal adjuvant. CTL elicited by peptide immunization afforded protection against RSV challenge, but also enhanced weight loss. CTL-mediated viral clearance was not dependent on IFN-γ since depletion using specific mAb during RSV challenge did not affect cellular recruitment or viral clearance. Depletion of IFN-γ did, however, reduce the concentration of TNF detected in lung homogenates of challenged mice and largely prevented the weight loss associated with CTL-mediated viral clearance. Mice primed with the attachment glycoprotein (G) develop lung eosinophilia after intranasal RSV challenge. Mucosal peptide vaccination reduced pulmonary eosinophilia in mice subsequently immunized with G and challenged with RSV. These studies emphasize that protective and immunoregulatory CD8+ CTL responses can be mucosally elicited using enterotoxin-based mucosal adjuvants but that resistance against viral infection may be accompanied by enhanced disease.
AB - In an effort to develop a safe and effective vaccine against respiratory syncytial virus (RSV), we used Escherichia coli heat-labile toxin (LT), and LTK63 (an LT mutant devoid of ADP-ribosyltransferase activity) to elicit murine CD8+ CTL responses to an intranasally codelivered CTL peptide from the second matrix protein (M2) of RSV. M282-90-specific CD8+ T cells were detected by IFN-γ enzyme-linked immunospot and 51Cr release assay in local and systemic lymph nodes, and their induction was dependent on the use of a mucosal adjuvant. CTL elicited by peptide immunization afforded protection against RSV challenge, but also enhanced weight loss. CTL-mediated viral clearance was not dependent on IFN-γ since depletion using specific mAb during RSV challenge did not affect cellular recruitment or viral clearance. Depletion of IFN-γ did, however, reduce the concentration of TNF detected in lung homogenates of challenged mice and largely prevented the weight loss associated with CTL-mediated viral clearance. Mice primed with the attachment glycoprotein (G) develop lung eosinophilia after intranasal RSV challenge. Mucosal peptide vaccination reduced pulmonary eosinophilia in mice subsequently immunized with G and challenged with RSV. These studies emphasize that protective and immunoregulatory CD8+ CTL responses can be mucosally elicited using enterotoxin-based mucosal adjuvants but that resistance against viral infection may be accompanied by enhanced disease.
UR - http://www.scopus.com/inward/record.url?scp=0035863815&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.166.2.1106
DO - 10.4049/jimmunol.166.2.1106
M3 - Article
C2 - 11145691
AN - SCOPUS:0035863815
VL - 166
SP - 1106
EP - 1113
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 2
ER -