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Vaccine. 2010 May 14;28(22):3801-8. doi: 10.1016/j.vaccine.2010.03.032. Epub 2010 Mar 31.

Single mucosal immunization of recombinant adenovirus-based vaccine expressing F1 protein fragment induces protective mucosal immunity against respiratory syncytial virus infection.

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  • 1Division of Life & Pharmaceutical Sciences, and the Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, 11-1 Dae-Hyun Dong, Seo-Dae-Mun Gu, Seoul 120-750, Republic of Korea.

Abstract

Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract disease in infancy and early childhood. Despite its importance as a pathogen, there is no licensed vaccine against RSV. The fusion (F) protein of RSV is a potentially important target for protective antiviral immune responses. Here, we studied the immune responses elicited by recombinant replication-deficient adenovirus (rAd)-based vaccines expressing the soluble F1 fragment of F protein (amino acids 155-524) in murine model. The expression of secreted F1 fragment by rAd was significantly increased by codon optimization. Strong mucosal IgA response was induced by single intranasal immunization of codon-optimized vaccine, rAd/F1co, but not by rAd/F1wt. A single intranasal immunization with rAd/F1co provided potent protection against subsequent RSV challenge. Interestingly, neither serum Ig nor T-cell response directed to F protein was detected in the rAd/F1co-immune mice, suggesting that protective immunity by rAd/F1co is mainly mediated through mucosal IgA induction. Indeed, co-delivery of cholera toxin B subunit significantly enhanced mucosal IgA responses by the optimized vaccine, which correlates with protective efficacy. Taken together, our data demonstrate that a single intranasal administration of rAd/F1co is sufficient for the protection and represents a promising prophylactic vaccination regimen against RSV infection.

Copyright 2010 Elsevier Ltd. All rights reserved.

PMID:
20362203
[PubMed - indexed for MEDLINE]
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