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Active and passive immunization protects against lethal, extreme drug resistant-Acinetobacter baumannii infection

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).

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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.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Luo, G
Lin, L
Ibrahim, AS
Baquir, B
Pantapalangkoor, P
Bonomo, RA
Doi, Yyod4@pitt.eduYOD4
Adams, MD
Russo, TA
Spellberg, B
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorFilion, Lionel G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 10 January 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 1
DOI or Unique Handle: 10.1371/journal.pone.0029446
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Refereed: Yes
MeSH Headings: Acinetobacter Infections--immunology; Acinetobacter Infections--microbiology; Acinetobacter Infections--prevention & control; Acinetobacter baumannii--immunology; Acinetobacter baumannii--isolation & purification; Amino Acid Sequence; Animals; Antibodies, Bacterial--immunology; Antibody Formation--immunology; Antibody Specificity--immunology; Bacterial Outer Membrane Proteins--chemistry; Bacterial Outer Membrane Proteins--immunology; Bacterial Vaccines--immunology; Conserved Sequence; Disease Models, Animal; Drug Resistance, Bacterial--immunology; Humans; Immune Sera; Immunity, Humoral--immunology; Immunization; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Sepsis--immunology; Sepsis--microbiology; Vaccination
Other ID: NLM PMC3254619
PubMed Central ID: PMC3254619
PubMed ID: 22253723
Date Deposited: 13 Sep 2012 15:26
Last Modified: 29 Jan 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/14013

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