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Infect. Immun. doi:10.1128/IAI.01668-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. 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

Virology Laboratory, Bacteriology Laboratory, Pathology Service, Ricardo Gutiérrez Children Hospital, Buenos Aires, Argentina; Infectious Diseases Research Group, Siebens-Drake Medical Research Institute, Departments of Microbiology and Immunology, and Medicine, University of Western Ontario, London, Ontario, Canada N6A 5C1

^* To whom correspondence should be addressed. Email: gmbertot{at}yahoo.com.ar.

	Abstract

Chronic lung infection by opportunistic pathogens, such as Pseudomonas aeruginosa and members of the Burkholderia cepacia complex (Bcc), 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 of intranasal vaccination in mice using 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 demonstrated enhanced clearance of B. multivorans from the lungs of vaccinated animals, which correlated with OMPs-specific secretory IgA responses. Furthermore, OMPs-immunized mice showed a 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 OMPs vaccine conferred protection against B. cenocepacia challenge in this mouse infection model, suggesting that OMPs afford cross-protection ability against B. cepacia complex. We therefore conclude 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 an increased mucosal immunity in the airways may benefit patients with cystic fibrosis.