Mucosal delivery of a respiratory syncytial virus CTL peptide with enterotoxin-based adjuvants elicits protective, immunopathogenic, and immunoregulatory antiviral CD8+ T cell responses

C. P. Simmons, T. Hussell, T. Sparer, G. Walzl, P. Openshaw, G. Dougan

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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.
    Original languageEnglish
    Pages (from-to)1106-1113
    Number of pages7
    JournalJournal of Immunology
    Volume166
    Issue number2
    Publication statusPublished - 15 Jan 2001

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