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 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.
Bertot
Gustavo M
GM
Laboratorio de Virología, Hospital de Niños Ricardo Gutiérrez, Gallo 1330, 1425 Buenos Aires, Argentina. gmbertot@yahoo.com.ar
Restelli
Marcela A
MA
Galanternik
Laura
L
Aranibar Urey
Rene C
RC
Valvano
Miguel A
MA
Grinstein
Saúl
S
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000547:Amantadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage* / Q000276:immunology; D019121:Burkholderia Infections / Q000276:immunology / Q000517:prevention & control*; D042602:Burkholderia cepacia complex / Q000737:chemistry*; D004151:Dipeptides / Q000008:administration & dosage* / Q000276:immunology; D004195:Disease Models, Animal; D007114:Immunization; D008171:Lung Diseases / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D004151:Dipeptides; C044891:adamantylamide-alanyl-isoglutamine; D000547:Amantadine