Inhibition of STAT6 during vaccination with formalin-inactivated RSV prevents induction of Th2-cell-biased airway disease.
Eur J Immunol
; 44(8): 2349-59, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-24796717
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírus Sinciciais Respiratórios
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Infecções por Vírus Respiratório Sincicial
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Células Th2
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Vacinas contra Vírus Sincicial Respiratório
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Fator de Transcrição STAT6
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Canadá