eprintid: 14013 rev_number: 19 userid: 677 importid: 607 dir: disk0/00/01/40/13 datestamp: 2012-09-13 15:26:03 lastmod: 2019-01-29 15:55:43 status_changed: 2012-09-13 15:26:03 type: article metadata_visibility: show contact_email: bspellberg@labiomed.org item_issues_count: 0 eprint_status: archive creators_name: Luo, G creators_name: Lin, L creators_name: Ibrahim, AS creators_name: Baquir, B creators_name: Pantapalangkoor, P creators_name: Bonomo, RA creators_name: Doi, Y creators_name: Adams, MD creators_name: Russo, TA creators_name: Spellberg, B creators_email: creators_email: creators_email: creators_email: creators_email: creators_email: creators_email: yod4@pitt.edu creators_email: creators_email: creators_email: creators_id: creators_id: creators_id: creators_id: creators_id: creators_id: creators_id: YOD4 creators_id: creators_id: creators_id: contributors_type: http://www.loc.gov/loc.terms/relators/EDT contributors_name: Filion, Lionel G. title: Active and passive immunization protects against lethal, extreme drug resistant-Acinetobacter baumannii infection ispublished: pub divisions: sch_gsph_infectiousdiseasesmicrobiology full_text_status: public abstract: Extreme-drug-resistant (XDR) Acinetobacter baumannii is a rapidly emerging pathogen causing infections with unacceptably high mortality rates due to inadequate available treatment. New methods to prevent and treat such infections are a critical unmet medical need. To conduct a rational vaccine discovery program, OmpA was identified as the primary target of humoral immune response after intravenous infection by A. baumannii in mice. OmpA was >99% conserved at the amino acid level across clinical isolates harvested between 1951 and 2009 from cerebrospinal fluid, blood, lung, and wound infections, including carbapenem-resistant isolates, and was ≥89% conserved among other sequenced strains, but had minimal homology to the human proteome. Vaccination of diabetic mice with recombinant OmpA (rOmpA) with aluminum hydroxide adjuvant markedly improved survival and reduced tissue bacterial burden in mice infected intravenously. Vaccination induced high titers of anti-OmpA antibodies, the levels of which correlated with survival in mice. Passive transfer with immune sera recapitulated protection. Immune sera did not enhance complement-mediated killing but did enhance opsonophagocytic killing of A. baumannii. These results define active and passive immunization strategies to prevent and treat highly lethal, XDR A. baumannii infections. © 2012 Luo et al. date: 2012-01-10 date_type: published publication: PLoS ONE volume: 7 number: 1 refereed: TRUE id_number: 10.1371/journal.pone.0029446 other_id: NLM PMC3254619 pmcid: PMC3254619 pmid: 22253723 mesh_headings: Acinetobacter Infections--immunology mesh_headings: Acinetobacter Infections--microbiology mesh_headings: Acinetobacter Infections--prevention & control mesh_headings: Acinetobacter baumannii--immunology mesh_headings: Acinetobacter baumannii--isolation & purification mesh_headings: Amino Acid Sequence mesh_headings: Animals mesh_headings: Antibodies, Bacterial--immunology mesh_headings: Antibody Formation--immunology mesh_headings: Antibody Specificity--immunology mesh_headings: Bacterial Outer Membrane Proteins--chemistry mesh_headings: Bacterial Outer Membrane Proteins--immunology mesh_headings: Bacterial Vaccines--immunology mesh_headings: Conserved Sequence mesh_headings: Disease Models, Animal mesh_headings: Drug Resistance, Bacterial--immunology mesh_headings: Humans mesh_headings: Immune Sera mesh_headings: Immunity, Humoral--immunology mesh_headings: Immunization mesh_headings: Mice mesh_headings: Mice, Inbred BALB C mesh_headings: Molecular Sequence Data mesh_headings: Sepsis--immunology mesh_headings: Sepsis--microbiology mesh_headings: Vaccination chemical_names: Antibodies, Bacterial chemical_names: Bacterial Outer Membrane Proteins chemical_names: Bacterial Vaccines chemical_names: Immune Sera chemical_names: OMPA outer membrane proteins citation: Luo, G and Lin, L and Ibrahim, AS and Baquir, B and Pantapalangkoor, P and Bonomo, RA and Doi, Y and Adams, MD and Russo, TA and Spellberg, B (2012) Active and passive immunization protects against lethal, extreme drug resistant-Acinetobacter baumannii infection. PLoS ONE, 7 (1). document_url: http://d-scholarship-dev.library.pitt.edu/14013/1/Active_and_Passive_Immunization.pdf document_url: http://d-scholarship-dev.library.pitt.edu/14013/8/licence.txt