Immunization with lipopolysaccharide-deficient whole cells provides protective immunity in an experimental mouse model of Acinetobacter baumannii infection

PLoS One. 2014 Dec 8;9(12):e114410. doi: 10.1371/journal.pone.0114410. eCollection 2014.

Abstract

The increasing clinical importance of infections caused by multidrug resistant Acinetobacter baumannii warrants the development of novel approaches for prevention and treatment. In this context, vaccination of certain patient populations may contribute to reducing the morbidity and mortality caused by this pathogen. Vaccines against Gram-negative bacteria based on inactivated bacterial cells are highly immunogenic and have been shown to produce protective immunity against a number of bacterial species. However, the high endotoxin levels present in these vaccines due to the presence of lipopolysaccharide complicates their use in human vaccination. In the present study, we used a laboratory-derived strain of A. baumannii that completely lacks lipopolysaccharide due to a mutation in the lpxD gene (IB010), one of the genes involved in the first steps of lipopolysaccharide biosynthesis, for vaccination. We demonstrate that IB010 has greatly reduced endotoxin content (<1.0 endotoxin unit/106 cells) compared to wild type cells. Immunization with formalin inactivated IB010 produced a robust antibody response consisting of both IgG1 and IgG2c subtypes. Mice immunized with IB010 had significantly lower post-infection tissue bacterial loads and significantly lower serum levels of the pro-inflammatory cytokines IL-1β, TNF-α and IL-6 compared to control mice in a mouse model of disseminated A. baumannii infection. Importantly, immunized mice were protected from infection with the ATCC 19606 strain and an A. baumannii clinical isolate. These data suggest that immunization with inactivated A. baumannii whole cells deficient in lipopolysaccharide could serve as the basis for a vaccine for the prevention of infection caused by A. baumannii.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter Infections / immunology
  • Acinetobacter Infections / microbiology
  • Acinetobacter Infections / prevention & control*
  • Acinetobacter baumannii / immunology*
  • Animals
  • Bacterial Load
  • Bacterial Vaccines / therapeutic use*
  • Disease Models, Animal
  • Female
  • Humans
  • Immunization
  • Lipopolysaccharides / deficiency*
  • Lipopolysaccharides / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Sepsis / immunology
  • Sepsis / microbiology
  • Sepsis / prevention & control*

Substances

  • Bacterial Vaccines
  • Lipopolysaccharides

Grants and funding

Support was provided by REIPI REIPI RD06/0008/0000 Consejería de Salud de la Junta de Andalucía (PI-0046-2011) Subprograma Miguel Servet from the Ministerio de Economía y Competitividad of Spain (CP11/00314). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.