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See 1 citation in Eur J Immunol 2014 by Srinivasa:

Eur J Immunol. 2014 Aug;44(8):2349-59. doi: 10.1002/eji.201344206. Epub 2014 Jun 5.

Inhibition of STAT6 during vaccination with formalin-inactivated RSV prevents induction of Th2-cell-biased airway disease.

Author information

1
Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC, Canada.

Abstract

The pattern of immune response to a vaccine antigen can influence both efficacy and adverse events. Th2-cell-deviated responses have been implicated in both human and murine susceptibility to enhanced disease following formalin-inactivated (FI) vaccines for measles and RSV. In this study, we used the Th2-cell-deviated murine model of FI-RSV vaccination to test the ability of a dominant negative, cell-penetrating peptide inhibitor of STAT6 (STAT6 inhibitory peptide (IP)) to modulate the vaccine-induced predisposition to exaggerated inflammation during later RSV infection. Intranasal delivery of STAT6-IP in BALB/c mice at the time of distal intramuscular FI-RSV vaccination (Early Intervention) markedly decreased vaccine-enhanced, Th2-cell-dependent pathology upon subsequent RSV challenge. Administration of the STAT6-IP at the time of RSV challenge (Late Intervention) had no effect. Following RSV challenge, the STAT6-IP-treated mice in the Early Intervention group had lower airway eosinophils, increased lung IFN-γ levels, as well as increased IFN-γ-secreting CD4(+) and CD8(+) cells in the lungs. Our findings demonstrate the feasibility of targeting intracellular signaling pathways as a new way to modulate vaccine-induced responses.

KEYWORDS:

Formalin-inactivated RSV vaccine; Respiratory syncytial virus; STAT6; STAT6-inhibitory peptide; Vaccine-enhanced disease

PMID:
24796717
DOI:
10.1002/eji.201344206
[Indexed for MEDLINE]
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