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Cell-Free Scaled Production and Adjuvant Addition to a Recombinant Major Outer Membrane Protein from Chlamydia muridarum for Vaccine Development
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Codon usage bias in Chlamydia trachomatis and the effect of codon modification in the MOMP gene on immune responses

Yan Zheng1, Wei-Ming Zhao, Hong Wang

  • 1Department of Medical Microbiology, School of Medicine, Shandong University, Jinan, Shandong 250012, PR China.

Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire
|May 31, 2007
PubMed

Insights

Human codon optimization of Chlamydia trachomatis major outer-membrane protein (MOMP) significantly boosts protein expression and immune responses. This enhances the potential of C. trachomatis MOMP DNA vaccines in mammalian systems.

Area of Science:

  • Microbiology
  • Immunology
  • Molecular Biology

Background:

  • Chlamydia trachomatis is an obligate intracellular bacterium causing significant ocular and sexually transmitted infections.
  • Significant differences exist in codon usage patterns between C. trachomatis mouse pneumonitis biovar (MoPn) and Homo sapiens.
  • Enhancing Chlamydia protein expression in mammalian cells is crucial for vaccine development.

Purpose of the Study:

  • To investigate the effect of human codon optimization on the expression and immunogenicity of the C. trachomatis MoPn major outer-membrane protein (MOMP).
  • To compare the efficacy of a human codon-optimized MOMP DNA vaccine with the wild-type counterpart.

Main Methods:

  • DNA sequences encoding MoPn MOMP were modified using human-preferred codons.
  • Synthesized human-optimized and wild-type MOMP genes were cloned into expression vectors.
  • Protein expression levels, mRNA expression, and immunogenicity (antibody production, cellular responses) were assessed in vitro and in vivo using mouse models.

Main Results:

  • Human codon optimization led to significantly higher MOMP protein levels in mammalian cells, without altering mRNA levels.
  • Mice immunized with the human-optimized MOMP DNA vaccine exhibited enhanced antigen-specific IgG antibody production.
  • Stronger delayed-type hypersensitivity reactions, increased T cell proliferation, and higher interferon-gamma production were observed in mice immunized with the optimized construct.

Conclusions:

  • Human codon optimization is an effective strategy to enhance gene expression of C. trachomatis MOMP in mammalian systems.
  • Optimized MOMP DNA vaccination significantly improves immunogenicity, suggesting potential for more effective Chlamydia vaccines.
  • Codon optimization represents a promising approach for developing improved DNA vaccines against Chlamydia infections.

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