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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. M2(82-90)-specific CD8(+) T cells were detected by IFN-gamma enzyme-linked immunospot and (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(+) CTL responses can be mucosally elicited using enterotoxin-based mucosal adjuvants but that resistance against viral infection may be accompanied by enhanced disease.

Type

Journal article

Journal

J Immunol

Publication Date

15/01/2001

Volume

166

Pages

1106 - 1113

Keywords

Adjuvants, Immunologic, Administration, Intranasal, Animals, Bacterial Toxins, CD8-Positive T-Lymphocytes, Enterotoxins, Eosinophilia, Epitopes, T-Lymphocyte, Escherichia coli Proteins, Immunity, Innate, Interferon-gamma, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Nasal Mucosa, Peptide Fragments, Respiratory Syncytial Virus Infections, Respiratory Syncytial Virus, Human, Swine, T-Lymphocytes, Cytotoxic, Th2 Cells, Viral Proteins, Viral Vaccines