A combination of the TLR4 agonist CIA05 and alum promotes the immune responses to Bacillus anthracis protective antigen in mice

Int Immunopharmacol. 2011 Sep;11(9):1195-204. doi: 10.1016/j.intimp.2011.03.020. Epub 2011 Apr 12.

Abstract

Anthrax is an infectious disease caused by Bacillus anthracis. The currently licensed human anthrax vaccines contain protective antigen (PA) as a major protective component and alum as an adjuvant. In this study, we investigated whether CIA05, a TLR4 agonist, is able to promote the immune response to an anthrax vaccine adjuvanted with alum. BALB/c mice were immunized intraperitoneally three times at 2-week intervals with a recombinant B. anthracis PA alone or in combination with CIA05 in the absence or presence of alum, and immune responses were determined 2 or 3 weeks after the third immunization. The results showed that the combination of CIA05 and alum significantly increased both serum anti-PA IgG antibody and toxin-neutralizing antibody titers, and the adjuvant effects were greater when lower antigen doses were used for immunization. Both CIA05 and alum stimulated PA-specific splenocyte secretion of interleukin (IL)-4, IL-5, and IL-6. A combination of the two yielded synergistic effects on IL-4 secretion, but CIA05 tended to repress IL-5 and IL-6 secretions induced by alum. Co-administration of CIA05 and alum also increased GL7 expression in B220(+)CD24(+) splenic cells, indicating the ability to activate B cells. These data suggest that CIA05, combined with alum, could be used to achieve higher immune responses to PA, leading to the development of an effective anthrax vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Alum Compounds / pharmacology*
  • Animals
  • Anthrax / immunology
  • Anthrax / prevention & control
  • Anthrax Vaccines / administration & dosage
  • Anthrax Vaccines / immunology
  • Antibodies, Bacterial / blood
  • Antibodies, Bacterial / immunology
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antigens, Bacterial / immunology
  • Antigens, Differentiation / immunology
  • B-Lymphocytes / immunology
  • Bacillus anthracis / immunology*
  • Bacterial Toxins / immunology
  • Immunization / methods
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Interleukins / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Protective Agents / administration & dosage*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / immunology
  • Spleen / drug effects
  • Spleen / immunology
  • Toll-Like Receptor 4 / agonists*

Substances

  • Adjuvants, Immunologic
  • Alum Compounds
  • Anthrax Vaccines
  • Antibodies, Bacterial
  • Antibodies, Neutralizing
  • Antigens, Bacterial
  • Antigens, Differentiation
  • Bacterial Toxins
  • Immunoglobulin G
  • Interleukins
  • Protective Agents
  • Recombinant Proteins
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • anthrax toxin
  • antigen GL7
  • aluminum sulfate