Detoxification of endotoxin by aluminum hydroxide adjuvant

Yi Shi, Harm HogenEsch, Fred E. Regnier, Stanley L. Hem

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Langmuir adsorption isotherms of endotoxin and aluminum-containing adjuvants at pH 7.4 and 25°C revealed that aluminum hydroxide adjuvant has a greater adsorption capacity (283 μg/mg Al) and adsorption coefficient (1.3 × 104 ml/μg) than aluminum phosphate adjuvant (3.0 μg/mg Al, 0.20 ml/μg). The difference in endotoxin adsorption was related to two adsorption mechanisms: electrostatic attraction and covalent bonding. The isoelectric point (iep) of endotoxin is approximately 2. An electrostatic attractive force will be present with aluminum hydroxide adjuvant (iep=11.4), and an electrostatic repulsive force will operate with aluminum phosphate adjuvant (iep=4.6). Endotoxin contains two phosphate groups in the lipid A portion. Covalent bonding occurs with surface aluminum in aluminum hydroxide adjuvant but is inhibited by surface phosphate in aluminum phosphate adjuvant. In-vitro desorption experiments using components of interstitial fluid showed that endotoxin adsorbed by aluminum hydroxide adjuvant was not desorbed by interstitial anions (5 mM phosphate or 2.7 mM citrate) or interstitial proteins (25 mg albumin/ml). The effect of aluminum-containing adjuvants on the systemic response of Sprague-Dawley rats to a 15 μg/kg subcutaneous dose of endotoxin was determined by measuring the serum concentration of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). TNF-α and IL-6 were observed in the group which received an endotoxin solution or endotoxin and aluminum phosphate adjuvant. No TNF-α or IL-6 was detected in the group that received endotoxin and aluminum hydroxide adjuvant. Aluminum hydroxide adjuvant detoxifies endotoxin by adsorbing it in the vaccine and then not releasing it in interstitial fluid upon administration.

Original languageEnglish (US)
Pages (from-to)1747-1752
Number of pages6
JournalVaccine
Volume19
Issue number13-14
DOIs
StatePublished - Feb 8 2001
Externally publishedYes

Keywords

  • Adsorption isotherm
  • Aluminum hydroxide adjuvant
  • Desorption in interstitial fluid
  • Endotoxin detoxification

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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