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

Guanpingshen Luo, Lin Lin, Ashraf S. Ibrahim, Beverlie Baquir, Paul Pantapalangkoor, Robert A. Bonomo, Yohei Doi, Mark D. Adams, Thomas A. Russo, Brad Spellberg

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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.

Original languageEnglish
Article numbere29446
JournalPloS one
Volume7
Issue number1
DOIs
Publication statusPublished - 10-01-2012
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Luo, G., Lin, L., Ibrahim, A. S., Baquir, B., Pantapalangkoor, P., Bonomo, R. A., Doi, Y., Adams, M. D., Russo, T. A., & Spellberg, B. (2012). Active and passive immunization protects against lethal, extreme drug resistant-Acinetobacter baumannii infection. PloS one, 7(1), [e29446]. https://doi.org/10.1371/journal.pone.0029446