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Journal of Virology, December 2007, p. 13801-13808, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01246-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Protective Immunity to Pseudomonas aeruginosa Induced with a Capsid-Modified Adenovirus Expressing P. aeruginosa OprF{triangledown}

Stefan Worgall,1,2* Anja Krause,1 JianPing Qiu,1 Ju Joh,1 Neil R. Hackett,1 and Ronald G. Crystal1

Department of Genetic Medicine,1 Department of Pediatrics, Weill Medical College of Cornell University, New York, New York2

Received 7 June 2007/ Accepted 3 October 2007

This study focuses on the development of a new clinical vaccine candidate (AdOprF.RGD.Epi8) against Pseudomonas aeruginosa using an E1– E3– adenovirus (Ad) vector expressing OprF (AdOprF.RGD.Epi8) and modifications of the Ad genome providing two capsid changes: (i) modification of the Ad hexon gene to incorporate an immune-dominant OprF epitope (Epi8) into loop 1 of the hexon, enabling repeat administration to boost the anti-OprF immune response, and (ii) modification of the fiber gene to incorporate an integrin-binding RGD sequence to enhance gene delivery to antigen-presenting cells. Western analysis confirmed that AdOprF.RGD.Epi8 expresses OprF, contains Epi8 in the hexon protein, and enhances gene transfer to dendritic cells compared to AdOprF, a comparable Ad vector expressing OprF with an unmodified capsid. Intramuscular immunization of C57BL/6 mice with AdOprF.RGD.Epi8 resulted in the generation of anti-OprF antibodies at comparable levels to those induced following immunization with AdOprF, but immunization with AdOprF.RGD.Epi8 was associated with increased CD4 and CD8 gamma interferon T-cell responses against OprF as well as increased survival against lethal pulmonary challenge with agar-encapsulated P. aeruginosa. Importantly, repeat administration of AdOprF.RGD.Epi8 resulted in boosting of the humoral anti-OprF response as well as increased protection, whereas no boosting could be achieved with repeat administration of AdOprF. This suggests that the capsid-modified AdOprF.RGD.Epi8 vector is a more effective immunogen compared to a comparable wild-type Ad capsid, making it a good candidate for an anti-P. aeruginosa vaccine.

* Corresponding author. Mailing address: Department of Genetic Medicine, Weill Medical College of Cornell University, 1300 York Avenue, Box 96, New York, NY 10021. Phone: (646) 962-4363. Fax: (646) 962-0220. E-mail: geneticmedicine{at}med.cornell.edu

{triangledown} Published ahead of print on 17 October 2007.

Journal of Virology, December 2007, p. 13801-13808, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01246-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Weimer, E. T., Lu, H., Kock, N. D., Wozniak, D. J., Mizel, S. B. (2009). A Fusion Protein Vaccine Containing OprF Epitope 8, OprI, and Type A and B Flagellins Promotes Enhanced Clearance of Nonmucoid Pseudomonas aeruginosa. Infect. Immun. 77: 2356-2366 [Abstract] [Full Text]  


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