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Infection and Immunity, June 2007, p. 2740-2752, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.01668-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Nasal Immunization with Burkholderia multivorans Outer Membrane Proteins and the Mucosal Adjuvant Adamantylamide Dipeptide Confers Efficient Protection against Experimental Lung Infections with B. multivorans and B. cenocepacia{triangledown}

Gustavo M. Bertot,1* Marcela A. Restelli,1 Laura Galanternik,2 Rene C. Aranibar Urey,3 Miguel A. Valvano,4,5 and Saúl Grinstein1

Virology Laboratory,1 Bacteriology Laboratory,2 Pathology Service, Ricardo Gutiérrez Children's Hospital, Buenos Aires, Argentina,3 Infectious Diseases Research Group, Siebens-Drake Medical Research Institute, Department of Microbiology and Immunology,4 Department of Medicine, University of Western Ontario, London, Ontario N6A 5C1, Canada5

Received 18 October 2006/ Returned for modification 19 December 2006/ Accepted 30 January 2007

Chronic lung infection by opportunistic pathogens, such as Pseudomonas aeruginosa and members of the Burkholderia cepacia complex, is a major cause of morbidity and mortality in patients with cystic fibrosis. Outer membrane proteins (OMPs) of gram-negative bacteria are promising vaccine antigen candidates. In this study, we evaluated the immunogenicity, protection, and cross-protection conferred by intranasal vaccination of mice with OMPs from B. multivorans plus the mucosal adjuvant adamantylamide dipeptide (AdDP). Robust mucosal and systemic immune responses were stimulated by vaccination of naive animals with OMPs from B. multivorans and B. cenocepacia plus AdDP. Using a mouse model of chronic pulmonary infection, we observed enhanced clearance of B. multivorans from the lungs of vaccinated animals, which correlated with OMP-specific secretory immunoglobulin A responses. Furthermore, OMP-immunized mice showed rapid resolution of the pulmonary infection with virtually no lung pathology after bacterial challenge with B. multivorans. In addition, we demonstrated that administration of B. multivorans OMP vaccine conferred protection against B. cenocepacia challenge in this mouse infection model, suggesting that OMPs provide cross-protection against the B. cepacia complex. Therefore, we concluded that mucosal immunity to B. multivorans elicited by intranasal vaccination with OMPs plus AdDP could prevent early steps of colonization and infection with B. multivorans and also ameliorate lung tissue damage, while eliciting cross-protection against B. cenocepacia. These results support the notion that therapies leading to increased mucosal immunity in the airways may help patients with cystic fibrosis.

* Corresponding author. Mailing address: Laboratorio de Virología, Hospital de Niños Ricardo Gutiérrez, Gallo 1330, 1425 Buenos Aires, Argentina. Phone: 5411-4964-3118. Fax: 5411-4963-4122. E-mail: gmbertot{at}yahoo.com.ar

{triangledown} Published ahead of print on 12 February 2007.

Editor: V. J. DiRita

Infection and Immunity, June 2007, p. 2740-2752, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.01668-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Uehlinger, S., Schwager, S., Bernier, S. P., Riedel, K., Nguyen, D. T., Sokol, P. A., Eberl, L. (2009). Identification of Specific and Universal Virulence Factors in Burkholderia cenocepacia Strains by Using Multiple Infection Hosts. Infect. Immun. 77: 4102-4110 [Abstract] [Full Text]  


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