Skip to main content

The biological activity of a liposomal complete core lipopolysaccharide vaccine.

Publication ,  Journal Article
Erridge, C; Stewart, J; Bennett-Guerrero, E; McIntosh, TJ; Poxton, IR
Published in: J Endotoxin Res
2002

A vaccine that induces humoral immunity to lipopolysaccharide (LPS), while remaining non-pyrogenic should be beneficial, as high levels of antibodies against LPS are associated with a reduced risk of adverse outcome. However, pure LPS or bacteria expressing LPS are generally considered too toxic to be used as vaccines. Recently, a novel, immunogenic complete core lipopolysaccharide vaccine has been described, which has been designed to prevent endotoxin-related inflammatory reactions in surgical and high-risk hospitalized patients. In vivo studies have shown that while administration of the vaccine to rabbits results in no toxicity over 7 days, it does induce significantly enhanced antibody responses towards a broad range of clinically relevant Gram-negative LPSs. Here we show that encapsulation of the four complete core LPS types Escherichia coli K12, Escherichia coli R1, Bacteroides fragilis and Pseudomonas aeruginosa into liposomes greatly reduces the ability of a given amount of LPS to induce TNF-alpha production in vitro from human monocytes. In contrast to previous studies of liposomal LPS, we demonstrate a reduction in activity of approximately 100,000-fold; a reduction approximately 100-1,000-fold more than that previously described. The signalling by the liposomal LPS appears to be entirely dependent on serum factors, though this can be partially restored by soluble CD14 or, to a lesser extent, by lipopolysaccharide binding protein. Time-course experiments reveal that liposomal LPS signalling shows similar kinetics to pure LPS signalling. Therefore, as well as inducing specific antibody responses, liposomal LPS demonstrates characteristics suitable for use as a vaccine to be used in human beings.

Duke Scholars

Published In

J Endotoxin Res

ISSN

0968-0519

Publication Date

2002

Volume

8

Issue

1

Start / End Page

39 / 46

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Rabbits
  • Pseudomonas aeruginosa
  • Monocytes
  • Liposomes
  • Lipopolysaccharides
  • Immunology
  • Immunization
  • Humans
  • Escherichia coli
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Erridge, C., Stewart, J., Bennett-Guerrero, E., McIntosh, T. J., & Poxton, I. R. (2002). The biological activity of a liposomal complete core lipopolysaccharide vaccine. J Endotoxin Res, 8(1), 39–46.
Erridge, Clett, John Stewart, Elliott Bennett-Guerrero, Thomas J. McIntosh, and Ian R. Poxton. “The biological activity of a liposomal complete core lipopolysaccharide vaccine.J Endotoxin Res 8, no. 1 (2002): 39–46.
Erridge C, Stewart J, Bennett-Guerrero E, McIntosh TJ, Poxton IR. The biological activity of a liposomal complete core lipopolysaccharide vaccine. J Endotoxin Res. 2002;8(1):39–46.
Erridge, Clett, et al. “The biological activity of a liposomal complete core lipopolysaccharide vaccine.J Endotoxin Res, vol. 8, no. 1, 2002, pp. 39–46.
Erridge C, Stewart J, Bennett-Guerrero E, McIntosh TJ, Poxton IR. The biological activity of a liposomal complete core lipopolysaccharide vaccine. J Endotoxin Res. 2002;8(1):39–46.

Published In

J Endotoxin Res

ISSN

0968-0519

Publication Date

2002

Volume

8

Issue

1

Start / End Page

39 / 46

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Rabbits
  • Pseudomonas aeruginosa
  • Monocytes
  • Liposomes
  • Lipopolysaccharides
  • Immunology
  • Immunization
  • Humans
  • Escherichia coli