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Ag85B of Mycobacteria Elicits Effective CTL Responses through Activation of Robust Th1 Immunity as a Novel Adjuvant in DNA Vaccine¹

Shiki Takamura^*,, Kazuhiro Matsuo^,¶, Yutaka Takebe and Yasuhiro Yasutomi^2,

^* Japanese Foundation for AIDS Prevention, Tokyo, Japan; Department of Bioregulation, Mie University School of Medicine, Mie, Japan; Vaccine Research and Development Group and Laboratory of Molecular Virology and Epidemiology, AIDS Research Center, National Institute of Infectious Disease, Tokyo, Japan; and ^¶ Japan Science and Technology, Saitama, Japan

CD4⁺ T cells play a crucial role in CTL generation in a DNA vaccination strategy. Several studies have demonstrated the requirement of CD4⁺ T cells for the induction of a sufficient immune response by coadministrating DNAs. In the present study we investigated the effectiveness of Ag85B of mycobacteria, which is known to be one of the immunogenic proteins for Th1 development, as an adjuvant of a DNA vaccine. HIV gp120 DNA vaccine mixed with Ag85B DNA as an adjuvant induced HIV gp120-specific Th1 responses, as shown by delayed-type hypersensitivity, cytokine secretion, and increasing HIV-specific CTL responses. Moreover, these responses were enhanced in mice primed with Mycobacterium bovis bacillus Calmette-Guérin before immunization of HIV DNA vaccine mixed with Ag85B DNA. Furthermore, these immunized mice showed substantial reduction of HIV gp120-expressing recombinant vaccinia virus titers compared with the titers in other experimental mice after recombinant vaccinia virus challenge. Because most humans have been sensitized by spontaneous infection or by vaccination with mycobacteria, these findings indicate that Ag85B is a promising adjuvant for enhancing CTL responses in a DNA vaccination strategy.