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Journal of Virology, March 2008, p. 2350-2357, Vol. 82, No. 5
0022-538X/08/$08.00+0     doi:10.1128/JVI.02372-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Single Intranasal Immunization with Recombinant Adenovirus-Based Vaccine Induces Protective Immunity against Respiratory Syncytial Virus Infection{triangledown}

Jae-Rang Yu, Sol Kim, Jee-Boong Lee, and Jun Chang*

Division of Life and Pharmaceutical Sciences, Ewha Womans University, 11-1 Dae-Hyun Dong, Seo-Dae-Mun Gu, Seoul 120-750, Korea

Received 2 November 2007/ Accepted 6 December 2007

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 G glycoprotein of RSV, a major attachment protein, is a potentially important target for protective antiviral immune responses. Here, a recombinant replication-deficient adenovirus-based vaccine, rAd/3xG, expressing the soluble core domain of G glycoprotein (amino acids 130 to 230) engineered by codon optimization and tandem repetition for higher-level expression, was constructed and evaluated for its potential as an RSV vaccine in a murine model. A single intranasal immunization with rAd/3xG provided potent protection against RSV challenge which lasted for more than 10 weeks. Strong mucosal immunoglobulin A responses were also induced by a single intranasal immunization but not by intramuscular or oral administration of rAd/3xG. Interestingly, neither gamma interferon- nor interleukin-4-producing CD4 T cells directed to I-Ed-restricted epitope were detected in the lungs of rAd/3xG-immune mice upon challenge, whereas priming with vaccinia virus expressing RSV G (vvG) elicited strong Th1/Th2 mixed CD4 T-cell responses. Lung eosinophilia and vaccine-induced weight loss were significantly lower in the rAd/3xG-immune group than in the vvG-primed group. Together, our data demonstrate that a single intranasal administration of rAd/3xG elicits beneficial protective immunity and represents a promising vaccine regimen against RSV infection.

* Corresponding author. Mailing address: College of Pharmacy, Ewha Womans University, 11-1 Dae-Hyun Dong, Seo-Dae-Mun Gu, Seoul 120-750, Korea. Phone: 82-2-3277-2549. Fax: 82-2-3277-3051. E-mail: tcell{at}ewha.ac.kr

{triangledown} Published ahead of print on 19 December 2007.

Journal of Virology, March 2008, p. 2350-2357, Vol. 82, No. 5
0022-538X/08/$08.00+0     doi:10.1128/JVI.02372-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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