title: Active and passive immunization protects against lethal, extreme drug resistant-Acinetobacter baumannii infection.
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.
authors.affiliation: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, California, United States of America.
authors.forename: Guanpingshen
authors.initials: G
authors.lastname: Luo
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.forename: Ashraf S
authors.initials: AS
authors.lastname: Ibrahim
authors.forename: Beverlie
authors.initials: B
authors.lastname: Baquir
authors.forename: Paul
authors.initials: P
authors.lastname: Pantapalangkoor
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bonomo
authors.forename: Yohei
authors.initials: Y
authors.lastname: Doi
authors.forename: Mark D
authors.initials: MD
authors.lastname: Adams
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Russo
authors.forename: Brad
authors.initials: B
authors.lastname: Spellberg
mesh_terms: D000151:Acinetobacter Infections / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D040981:Acinetobacter baumannii / Q000276:immunology* / Q000302:isolation & purification; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology; D017124:Conserved Sequence; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial / Q000276:immunology*; D006801:Humans; D007106:Immune Sera; D056724:Immunity, Humoral / Q000276:immunology; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D018805:Sepsis / Q000276:immunology / Q000382:microbiology; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D007106:Immune Sera; C078167:OMPA outer membrane proteins