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Journal of Virology, December 2009, p. 12601-12610, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.01036-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Protective Efficacy and Immunogenicity of an Adenoviral Vector Vaccine Encoding the Codon-Optimized F Protein of Respiratory Syncytial Virus{triangledown}

Rebekka Kohlmann, Sarah Schwannecke, Bettina Tippler, Nicola Ternette,{dagger} Vladimir V. Temchura, Matthias Tenbusch, Klaus Überla, and Thomas Grunwald*

Department of Molecular and Medical Virology, Ruhr-Universitaet Bochum, Bochum, Germany

Received 21 May 2009/ Accepted 17 September 2009

Adenoviral vectors (AdV) have received considerable attention for vaccine development because of their high immunogenicity and efficacy. In previous studies, it was shown that DNA immunization of mice with codon-optimized expression plasmids encoding the fusion protein of respiratory syncytial virus (RSV F) resulted in enhanced protection against RSV challenge compared to immunization with plasmids carrying the wild-type cDNA sequence of RSV F. In this study, we constructed AdV carrying the codon-optimized full-length RSV F gene (AdV-F) or the soluble form of the RSV F gene (AdV-Fsol). BALB/c mice were immunized twice with AdV-F or AdV-Fsol and challenged with RSV intranasally. Substantial levels of antibody to RSV F were induced by both AdV vaccines, with peak neutralizing-antibody titers of 1:900. Consistently, the viral loads in lung homogenates and bronchoalveolar lavage fluids were significantly reduced by a factor of more than 60,000. The protection against viral challenge could be measured even 8 months after the booster immunization. AdV-F and AdV-Fsol induced similar levels of immunogenicity and protective efficacy. Therefore, these results encourage further development of AdV vaccines against RSV infection in humans.

* Corresponding author. Mailing address: Department of Molecular and Medical Virology, Ruhr-Universitaet Bochum, Universitaetsstrasse 150, 44780 Bochum, Germany. Phone: 49-234-3224882. Fax: 49-234-3214352. E-mail: thomas.grunwald{at}ruhr-uni-bochum.de

{triangledown} Published ahead of print on 23 September 2009.

{dagger} Present address: Henry Wellcome Building for Molecular Physiology, Department of Clinical Medicine, Oxford, OX3 7BN Oxford, United Kingdom.

Journal of Virology, December 2009, p. 12601-12610, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.01036-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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