title: Outer membrane vesicles as an acellular vaccine against Acinetobacter baumannii.
abstract: Acinetobacter baumannii produces different types of infections including pneumonia, meningitis, and bloodstream infections. The optimal treatment of these infections has been complicated by the global emergence of multidrug resistant strains, requiring the development of novel approaches for treatment and prevention. Outer membrane vesicles are outpouchings of the bacterial outer membrane that are secreted from numerous pathogenic Gram-negative bacteria. In the present study, we describe the isolation of outer membrane vesicles from A. baumannii and their use as a vaccine in a mouse model of disseminated sepsis. Immunization produced a robust antibody response against multiple bacterial antigens which consisted of antigen-specific IgG and IgM. In addition, both IgG1 and IgG2c subtypes were produced by immunization. Immunized mice had lower tissue bacterial loads and lower serum levels of the pro-inflammatory cytokines IL-6 and IL-1β post-infection compared to control mice. Importantly, vaccination protected mice from challenge with the ATCC 19606 strain and provided protection against two clinical isolates, including a pan-resistant strain. These results indicate that vaccination with outer membrane vesicles may be a viable strategy for preventing A. baumannii infection.
authors.affiliation: Unit of Infectious Disease, Microbiology, and Preventive Medicine, Institute of Biomedicine of Sevilla (IBiS), University Hospital Virgen del Rocío/CSIC/University of Sevilla, 41013 Sevilla, Spain. mcconnell.mike75@gmail.com
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McConnell
authors.forename: Carlos
authors.initials: C
authors.lastname: Rumbo
authors.forename: Germán
authors.initials: G
authors.lastname: Bou
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Pachón
mesh_terms: D000151:Acinetobacter Infections / Q000276:immunology / Q000517:prevention & control*; D040981:Acinetobacter baumannii / Q000276:immunology*; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D058491:Bacterial Load / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D053583:Interleukin-1beta; D015850:Interleukin-6