Liposome delivery of Chlamydia muridarum major outer membrane protein primes a Th1 response that protects against genital chlamydial infection in a mouse model

J Infect Dis. 2008 Sep 1;198(5):758-67. doi: 10.1086/590670.

Abstract

Background: Immunity to chlamydia is thought to rely on interferon (IFN)-gamma-secreting T helper cells type 1 (Th1) with an additional effect of secreted antibodies. A need for Th1-polarizing adjuvants in experimental chlamydia vaccines has been demonstrated, and antigen conformation has also been reported as being important for raising protective immunity.

Methods: C57BL/6 mice vaccinated with native refolded Chlamydia muridarum major outer membrane protein (MOMP) adjuvanted with either Th1-promoting cationic adjuvant formulation 1 (CAF01) or T helper cells type 2-promoting aluminum hydroxide (alum) received a genital inoculation of 1.5 x 10(5) inclusion-forming units of C. muridarum. The role played by CD4(+) T cells in MOMP/CAF01-raised immunity was investigated by depleting CD4(+) T cells in vaccinated mice, and antigen conformation dependence was evaluated by vaccination with recombinant MOMP.

Results: Mice vaccinated with MOMP/alum displayed a strong anti-MOMP humoral response with high IgG1 titers, low levels of IFN-gamma and tumor necrosis factor (TNF)-alpha, and only a slight reduction in chlamydial load. Mice vaccinated with MOMP/CAF01 displayed high titers of IgG2b, IFN-gamma, and TNF-alpha and a profoundly reduced vaginal chlamydial load, compared with control mice. The protection was CD4(+) T cell dependent and was not dependent on MOMP conformation.

Conclusion: CAF01 adjuvant facilitates a protective anti-MOMP CD4(+) T cell response independent of MOMP conformation.

MeSH terms

  • Animals
  • Antibodies, Bacterial / biosynthesis
  • Antibodies, Bacterial / blood
  • Bacterial Outer Membrane Proteins / administration & dosage
  • Bacterial Outer Membrane Proteins / immunology*
  • Bacterial Vaccines / administration & dosage
  • Bacterial Vaccines / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Chlamydia Infections / immunology
  • Chlamydia Infections / prevention & control*
  • Chlamydia muridarum / immunology*
  • Chlamydia muridarum / metabolism
  • Cytokines / biosynthesis
  • Female
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / blood
  • Liposomes
  • Mice
  • Mice, Inbred C57BL
  • Salpingitis / pathology
  • Th1 Cells / immunology*
  • Vagina / microbiology

Substances

  • Antibodies, Bacterial
  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines
  • Cytokines
  • Immunoglobulin G
  • Liposomes