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Preparation and preclinical evaluation of a novel liposomal complete-core lipopolysaccharide vaccine.

Publication ,  Journal Article
Bennett-Guerrero, E; McIntosh, TJ; Barclay, GR; Snyder, DS; Gibbs, RJ; Mythen, MG; Poxton, IR
Published in: Infect Immun
November 2000

Our objective is to develop a prophylactic vaccine strategy that can be evaluated for surgical and other high-risk hospitalized patients. In this paper, we describe the preparation and preclinical evaluation of a liposomal complete-core lipopolysaccharide (LPS) vaccine that is nontoxic and broadly antigenic. Complete-core (Ra-chemotype) LPSs were isolated from four gram-negative bacterial strains (Escherichia coli K-12, E. coli R1, Pseudomonas aeruginosa PAC608, and Bacteroides fragilis), mixed together to form a cocktail of complete-core LPSs, and then incorporated into multilamellar liposomes consisting of dimyristoyl phosphatidyl choline, dimyristoyl phosphatidylglycerol, and cholesterol in a 4:1:4 molar ratio. The endotoxic activities of these LPS-containing liposomes were less than 0.1% of the endotoxicities of the original free LPSs as measured by the Limulus amoebocyte lysate assay. In vivo administration of liposomal complete-core LPS mixed with Al(OH)(3) to rabbits resulted in no pyrogenicity or overt toxicity over a 7-day period. In immunoblots, sera from rabbits following active immunization elicited cross-reactive antibodies to a large panel of rough and smooth LPSs from numerous clinically relevant gram-negative bacteria, including E. coli (serotypes O1, O4, O6, O8, O12, O15, O18, O75, O86, O157, and O111), P. aeruginosa (Fisher-Devlin serotypes 1, 2, and 3, which correspond to International Antigenic Typing Scheme types 6, 11, and 2, respectively), Klebsiella pneumoniae (serotypes O1, O2ab, and O3), B. fragilis, and Bacteroides vulgatus. Active immunization of mice with liposomal complete-core LPS provided protection against a lethal challenge with E. coli O18 LPS. The vaccine tested was nontoxic, nonpyrogenic, and immunogenic against a wide variety of pathogens found in clinical settings.

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Published In

Infect Immun

DOI

ISSN

0019-9567

Publication Date

November 2000

Volume

68

Issue

11

Start / End Page

6202 / 6208

Location

United States

Related Subject Headings

  • Rabbits
  • Microbiology
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Liposomes
  • Lipopolysaccharides
  • Immunization
  • Female
  • Bacterial Vaccines
 

Citation

APA
Chicago
ICMJE
MLA
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Bennett-Guerrero, E., McIntosh, T. J., Barclay, G. R., Snyder, D. S., Gibbs, R. J., Mythen, M. G., & Poxton, I. R. (2000). Preparation and preclinical evaluation of a novel liposomal complete-core lipopolysaccharide vaccine. Infect Immun, 68(11), 6202–6208. https://doi.org/10.1128/IAI.68.11.6202-6208.2000
Bennett-Guerrero, E., T. J. McIntosh, G. R. Barclay, D. S. Snyder, R. J. Gibbs, M. G. Mythen, and I. R. Poxton. “Preparation and preclinical evaluation of a novel liposomal complete-core lipopolysaccharide vaccine.Infect Immun 68, no. 11 (November 2000): 6202–8. https://doi.org/10.1128/IAI.68.11.6202-6208.2000.
Bennett-Guerrero E, McIntosh TJ, Barclay GR, Snyder DS, Gibbs RJ, Mythen MG, et al. Preparation and preclinical evaluation of a novel liposomal complete-core lipopolysaccharide vaccine. Infect Immun. 2000 Nov;68(11):6202–8.
Bennett-Guerrero, E., et al. “Preparation and preclinical evaluation of a novel liposomal complete-core lipopolysaccharide vaccine.Infect Immun, vol. 68, no. 11, Nov. 2000, pp. 6202–08. Pubmed, doi:10.1128/IAI.68.11.6202-6208.2000.
Bennett-Guerrero E, McIntosh TJ, Barclay GR, Snyder DS, Gibbs RJ, Mythen MG, Poxton IR. Preparation and preclinical evaluation of a novel liposomal complete-core lipopolysaccharide vaccine. Infect Immun. 2000 Nov;68(11):6202–6208.

Published In

Infect Immun

DOI

ISSN

0019-9567

Publication Date

November 2000

Volume

68

Issue

11

Start / End Page

6202 / 6208

Location

United States

Related Subject Headings

  • Rabbits
  • Microbiology
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Liposomes
  • Lipopolysaccharides
  • Immunization
  • Female
  • Bacterial Vaccines