Mycobacterial codon optimization enhances antigen expression and virus-specific immune responses in recombinant Mycobacterium bovis bacille Calmette-Guérin expressing human immunodeficiency virus type 1 Gag.

Masaru Kanekiyo; Kazuhiro Matsuo; Makiko Hamatake; Takaichi Hamano; Takeaki Ohsu; Sohkichi Matsumoto; Takeshi Yamada; Shudo Yamazaki; Atsuhiko Hasegawa; Naoki Yamamoto; Mitsuo Honda

doi:10.1128/jvi.79.14.8716-8723.2005

PubMed · 15994765

Mycobacterial codon optimization enhances antigen expression and virus-specific immune responses in recombinant Mycobacterium bovis bacille Calmette-Guérin expressing human immunodeficiency virus type 1 Gag.

Masaru Kanekiyo·Kazuhiro Matsuo·Makiko Hamatake·Takaichi Hamano·Takeaki Ohsu·Sohkichi Matsumoto·Takeshi Yamada·Shudo Yamazaki·Atsuhiko Hasegawa·Naoki Yamamoto·Mitsuo Honda

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Abstract

Although its potential for vaccine development is already known, the introduction of recombinant human immunodeficiency virus (HIV) genes to Mycobacterium bovis bacille Calmette-Guérin (BCG) has thus far elicited only limited responses. In order to improve the expression levels, we optimized the codon usage of the HIV type 1 (HIV-1) p24 antigen gene of gag (p24 gag) and established a codon-optimized recombinant BCG (rBCG)-p24 Gag which expressed a 40-fold-higher level of p24 Gag than did that of nonoptimized rBCG-p24 Gag. Inoculation of mice with the codon-optimized rBCG-p24 Gag elicited effective immunity, as evidenced by virus-specific lymphocyte proliferation, gamma interferon ELISPOT cell induction, and antibody production. In contrast, inoculation of animals with the nonoptimized rBCG-p24 Gag induced only low levels of immune responses. Furthermore, a dose as small as 0.01 mg of the codon-optimized rBCG per animal proved capable of eliciting immune responses, suggesting that even low doses of a codon-optimized rBCG-based vaccine could effectively elicit HIV-1-specific immune responses.

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AIDS Vaccines Amino Acid Sequence Animals Base Sequence CD4-Positive T-Lymphocytes Codon Female HIV Core Protein p24 Interferon-gamma Lymphocyte Activation Mice Mice, Inbred BALB C Molecular Sequence Data Mycobacterium bovis Vaccines, Synthetic Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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Masaru Kanekiyo, Kazuhiro Matsuo, Makiko Hamatake, Takaichi Hamano, Takeaki Ohsu, Sohkichi Matsumoto, Takeshi Yamada, Shudo Yamazaki, Atsuhiko Hasegawa, Naoki Yamamoto, Mitsuo Honda. 2005. Mycobacterial codon optimization enhances antigen expression and virus-specific immune responses in recombinant Mycobacterium bovis bacille Calmette-Guérin expressing human immunodeficiency virus type 1 Gag.. https://doi.org/10.1128/jvi.79.14.8716-8723.2005

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