Mucosal Delivery of a Respiratory Syncytial Virus CTL Peptide with Enterotoxin-Based Adjuvants Elicits Protective, Immunopathogenic, and Immunoregulatory Antiviral CD8 super(+) T Cell Responses

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 super(+) CTL responses to an intranasally codelivered CTL peptide f...

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Veröffentlicht in:The Journal of immunology (1950) 2001-01, Vol.166 (2), p.1106-1113
Hauptverfasser: Simmons, C P, Hussell, T, Sparer, T, Walzl, G, Openshaw, P, Dougan, G
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Sprache:eng
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Zusammenfassung: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 super(+) CTL responses to an intranasally codelivered CTL peptide from the second matrix protein (M2) of RSV. M2 sub(82-90)-specific CD8 super(+) T cells were detected by IFN- gamma enzyme-linked immunospot and super(51)Cr 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- gamma since depletion using specific mAb during RSV challenge did not affect cellular recruitment or viral clearance. Depletion of IFN- gamma 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 super(+) CTL responses can be mucosally elicited using enterotoxin-based mucosal adjuvants but that resistance against viral infection may be accompanied by enhanced disease.
ISSN:0022-1767