Optimization of codon usage enhances the immunogenicity of a DNA vaccine encoding mycobacterial antigen Ag85B.
In spite of its many other benefits, DNA vaccine is limited in its application by its insufficient immunogenicity. One promising approach for enhancing its immunogenicity is to maximize its expression in the immunized host. In the current study, we investigated whether codon optimization of the mycobacterial antigen Ag85B gene could enhance the expression and immunogenicity of the Ag85B DNA vaccine. We generated a synthetic humanized Ag85B (hAg85B) gene in which codon usage was optimized for expression in human cells. DNA plasmids with codon-optimized hAg85B increased the level of protein expression in vitro and in vivo. DNA vaccine with hAg85B induced stronger Th1-like and cytotoxic T-cell immune responses in BALB/c mice and generated higher protective immunity in a BALB/c mouse model of Mycobacterium tuberculosis aerosol infection than did the DNA vaccine with wild-type Ag85B. Therefore, our results suggest that codon optimization of mycobacterial antigens (e.g., Ag85B) could improve protein expression and thereby enhance the immunogenicity of DNA vaccines against M. tuberculosis.
Ko
Hyun-Jeong
HJ
Laboratory of Immunology and Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shillim-Dong, Kwanak-Gu, Seoul, 151-742, Republic of Korea.
Ko
Sung-Youl
SY
Kim
Yeon-Jeong
YJ
Lee
Eun-Gae
EG
Cho
Sang-Nae
SN
Kang
Chang-Yuil
CY
D000217:Acyltransferases / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D003062:Codon / Q000096:biosynthesis*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D003062:Codon; D019444:Vaccines, DNA; D007371:Interferon-gamma; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis