Role of alum in improving the immunogenicity of biodegradable polymer particle entrapped antigens

Eur J Pharm Sci. 2009 Aug 12;38(1):18-28. doi: 10.1016/j.ejps.2009.05.009. Epub 2009 May 23.

Abstract

This study was aimed at understanding the role of alum in improving the immunogenicity of biodegradable polymer particle entrapped antigens. Presence of alum formed a fine network around PLA particles holding them together and promoted attachment of higher number of particles on macrophage surface for a considerable period of time. Use of alum lowered the burst release of the entrapped antigen from particles and thereafter also reduced the cumulative release of antigen from particles. Apart from this, PLA microparticles alone induced macrophages to release TNF-alpha similar to that induced by alum. However admixture of PLA particles and alum enhanced the secretion of TNF-alpha from 876pg/ml at 6h to 3500pg/ml at 24h which was higher than that induced by alum adsorbed TT. Immunization with admixture of antigen loaded polylactide (PLA) microparticles (2-8microm) and alum improved the antibody titers almost twice than that achieved from particle alone in experimental animals. Single point immunization with particle entrapped antigens and alum also elicited antibody titers comparable to two doses of alum adsorbed tetanus toxoid (TT) or diphtheria toxoid (DT). Our results suggest that presence of alum acts in multiple ways to improve the antibody titers of polymer particles entrapped antigens. Such co-operative adjuvant action of alum and polymer particles can be exploited to improve the immunogenicity of other antigens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology
  • Aluminum Hydroxide / chemistry
  • Aluminum Hydroxide / immunology*
  • Aluminum Hydroxide / pharmacology
  • Animals
  • Antibody Formation / immunology
  • Antigens / administration & dosage*
  • Antigens / immunology*
  • Biological Availability
  • Cell Line
  • Cell Survival / drug effects
  • Cytokines / metabolism
  • Drug Carriers / chemistry
  • Drug Carriers / metabolism*
  • Drug Carriers / pharmacology
  • Female
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Electron, Scanning
  • Particle Size
  • Polyesters / chemistry*
  • Rats
  • Rats, Wistar
  • Tetanus Toxoid / administration & dosage
  • Tetanus Toxoid / immunology
  • Tetanus Toxoid / pharmacokinetics
  • Vaccination / methods
  • Vaccines / administration & dosage
  • Vaccines / chemistry
  • Vaccines / immunology

Substances

  • Adjuvants, Immunologic
  • Antigens
  • Cytokines
  • Drug Carriers
  • Immunoglobulin G
  • Polyesters
  • Tetanus Toxoid
  • Vaccines
  • poly(lactide)
  • Aluminum Hydroxide