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

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 cand...

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Bibliographic Details
Published in:	Infection and Immunity Vol. 75; no. 6; pp. 2740 - 2752
Main Authors:	Bertot, Gustavo M, Restelli, Marcela A, Galanternik, Laura, Aranibar Urey, Rene C, Valvano, Miguel A, Grinstein, Saúl
Format:	Journal Article
Language:	English
Published:	Washington, DC American Society for Microbiology 01-06-2007
Subjects:	Adjuvants, Immunologic - administration & dosage Administration, Intranasal Amantadine - administration & dosage Amantadine - analogs & derivatives Amantadine - immunology Animals Antibodies, Bacterial - blood Applied microbiology Bacterial Outer Membrane Proteins - administration & dosage Bacterial Outer Membrane Proteins - immunology Bacteriology Biological and medical sciences Burkholderia cepacia Burkholderia cepacia complex - chemistry Burkholderia Infections - immunology Burkholderia Infections - prevention & control Burkholderia multivorans Dipeptides - administration & dosage Dipeptides - immunology Disease Models, Animal Fundamental and applied biological sciences. Psychology Immunization Lung Diseases - immunology Lung Diseases - microbiology Lung Diseases - prevention & control Mice Mice, Inbred BALB C Microbial Immunity and Vaccines Microbiology Miscellaneous Pseudomonas aeruginosa Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) Immunization Membrane protein Microbiology Immunological adjuvant Mucosa Lung Bacteria Vaccine Burkholderia External membrane Respiratory system Immunity
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Summary:	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.
Bibliography:	http://iai.asm.org/ ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Editor: V. J. DiRita 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@yahoo.com.ar
ISSN:	0019-9567 1098-5522
DOI:	10.1128/IAI.01668-06