Department of Microbiology and Immunology, Biomedical Sciences, College of Medicine, Liver Research Institute, Seoul National University, Seoul, South Korea.
Department of Microbiology and Immunology, Biomedical Sciences, College of Medicine, Cancer Research Institute, Seoul National University, Seoul, South Korea.
Front Immunol. 2018 Mar 27;9:643. doi: 10.3389/fimmu.2018.00643. eCollection 2018.
Even though the rate of new human immunodeficiency virus type 1 (HIV-1) infections is gradually decreasing worldwide, an effective preventive vaccine for HIV-1 is still urgently needed. The recombinant BCG (rBCG) is promising for the development of an HIV-1 vaccine. Recently, we showed that a recombinant expressing HIV-1 gag in a pMyong2 vector system (rSmeg-pMyong2-p24) increased the efficacy of a vaccine against HIV-1 in mice. Here, we evaluated the potential of an rBCG expressing HIV-1 p24 antigen Gag in pMyong2 (rBCG-pMyong2-p24) in a vaccine application for HIV-1 infection. We found that rBCG-pMyong2-p24 elicited an enhanced HIV-1 p24 Gag expression in rBCG and infected antigen-presenting cells. We also found that compared to rBCG-pAL-p24 in a pAL5000 derived vector system, rBCG-pMyong2-p24 elicited enhanced p24-specific immune responses in vaccinated mice as evidenced by higher levels of HIV-1 Gag-specific CD4 and CD8 T lymphocyte proliferation, gamma interferon ELISPOT cell induction, antibody production, and cytotoxic T lymphocytes (CTL) responses. Furthermore, rBCG-pMyong2-p24 showed a higher level of p24-specific Ab production than rSmeg-pMyong2-p24 in the same pMyong2 vector system. In conclusion, our data indicated that a live recombinant BCG expressing HIV-1 Gag using a pMyong2 vector system, rBCG-pMyong2-p24 elicited an enhanced immune response against HIV-1 infections in a mouse model system. So, rBCG-pMyong2-p24 may have the potential as a prime vaccine in a heterologous prime-boost vaccine strategy for HIV-1 infection.
尽管全球新的人类免疫缺陷病毒 1 型(HIV-1)感染率正在逐渐下降,但仍急需有效的预防性 HIV-1 疫苗。重组卡介苗(rBCG)是开发 HIV-1 疫苗的有希望的候选者。最近,我们发现,在 pMyong2 载体系统中表达 HIV-1 gag 的重组 rSmeg-pMyong2-p24 增加了针对 HIV-1 的疫苗在小鼠中的功效。在这里,我们评估了在 HIV-1 感染疫苗应用中,在 pMyong2 中表达 HIV-1 p24 抗原 Gag 的 rBCG 的潜力。我们发现,rBCG-pMyong2-p24 在 rBCG 和感染的抗原呈递细胞中引发了增强的 HIV-1 p24 Gag 表达。我们还发现,与在源自 pAL5000 的载体系统中的 rBCG-pAL-p24 相比,rBCG-pMyong2-p24 在接种疫苗的小鼠中引发了增强的 p24 特异性免疫反应,这表现为更高水平的 HIV-1 Gag 特异性 CD4 和 CD8 T 淋巴细胞增殖、γ干扰素 ELISPOT 细胞诱导、抗体产生和细胞毒性 T 淋巴细胞(CTL)反应。此外,rBCG-pMyong2-p24 在相同的 pMyong2 载体系统中显示出比 rSmeg-pMyong2-p24 更高水平的 p24 特异性 Ab 产生。总之,我们的数据表明,使用 pMyong2 载体系统表达 HIV-1 Gag 的活重组 BCG,rBCG-pMyong2-p24 在小鼠模型系统中引发了针对 HIV-1 感染的增强免疫反应。因此,rBCG-pMyong2-p24 可能有潜力作为 HIV-1 感染的异源初免-加强疫苗策略中的初级疫苗。