Takeda Satoshi, Shiosaki Kouichi, Kaneda Yasufumi, Nakasatomi Tetsuya, Yoshizaki Hitomi, Someya Kenji, Konno Yusuke, Eda Yasuyuki, Kino Youichirou, Yamamoto Naoki, Honda Mitsuo
AIDS Research Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Clin Immunol. 2004 Jul;112(1):92-105. doi: 10.1016/j.clim.2004.04.001.
By using the hepatitis B core (HBc) protein gene as a carrier, HIV-1 env V3 gene was inserted into the carrier gene, and the HIV gene was expressed inside a chimeric HIV-HBc particle (HIV-HBc), which was a unique candidate for induction of HIV-specific CTL activity. This was seen significantly in mice without the need of an adjuvant, because other responses specific for the HIV peptide such as T-cell proliferation and antibody production were not induced. However, when hemagglutinating virus of Japan (HVJ) protein was incorporated into an anionic liposome containing HIV peptide (HIV-HVJ-liposome) and was used as a booster immunization in HIV-HBc primed animals, the HIV-specific T-cell response and enhanced CTL activity were clearly induced in consecutively immunized animals. Furthermore, the HIV-specific humoral immune response was also induced and a neutralization activity was detected in the immune sera. Thus, when an HIV peptide antigen is expressed inside the virus like a particle of HBc, it can induce both cellular and humoral immunities when an HVJ-HIV-liposome, but not an HIV-liposome, is inoculated as the booster antigen. The HVJ-stimulated splenocytes secreted IL-18 and IL-12 to synergistically enhance the secretion of IFN-gamma in vitro. These findings suggest that the HVJ protein is effective at inducing the HIV-specific immunities, if used as part of a booster antigen in the consecutive immunization regimen.
通过使用乙肝核心(HBc)蛋白基因作为载体,将HIV-1 env V3基因插入载体基因中,HIV基因在嵌合HIV-HBc颗粒(HIV-HBc)内表达,该颗粒是诱导HIV特异性CTL活性的独特候选物。在小鼠中无需佐剂即可显著观察到这一点,因为未诱导出针对HIV肽的其他特异性反应,如T细胞增殖和抗体产生。然而,当将日本血凝病毒(HVJ)蛋白掺入含有HIV肽的阴离子脂质体(HIV-HVJ-脂质体)中,并用作HIV-HBc初免动物的加强免疫时,在连续免疫的动物中明显诱导出HIV特异性T细胞反应和增强的CTL活性。此外,还诱导出HIV特异性体液免疫反应,并在免疫血清中检测到中和活性。因此,当HIV肽抗原在类似HBc颗粒的病毒内部表达时,以HVJ-HIV-脂质体而非HIV-脂质体作为加强抗原接种时,可诱导细胞免疫和体液免疫。HVJ刺激的脾细胞在体外分泌IL-18和IL-12,协同增强IFN-γ的分泌。这些发现表明,如果在连续免疫方案中用作加强抗原的一部分,HVJ蛋白在诱导HIV特异性免疫方面是有效的。