Bolhassani Azam, Kardani Kimia, Vahabpour Rouhollah, Habibzadeh Nourieh, Aghasadeghi Mohammad Reza, Sadat Seyed Mehdi, Agi Elnaz
Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.
Department of Biotechnology, Faculty of Advanced Sciences and Technology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.
Immunol Lett. 2015 Dec;168(2):366-73. doi: 10.1016/j.imlet.2015.10.012. Epub 2015 Oct 27.
Development of an effective vaccine against HIV-1 infection is a main concern in worldwide. A potent vaccine for HIV-1 requires the induction and maintenance of both humoral and cellular immunity. In this study, the levels of humoral and cellular immune responses were compared using MPER-V3 injection in three immunization strategies such as DNA/DNA, peptide/peptide, and DNA/peptide (prime-boost). MPG peptide and Montanide 720 were used as a DNA delivery system, and as a peptide adjuvant, respectively. Our results demonstrated that MPG forms stable non-covalent nanoparticles with plasmid DNA at N/P ratio of 10:1 (∼ 110-130 nm). The in vitro transfection efficiency of MPER-V3 DNA using MPG was comparable with lipofectamine and turbofect reagents as a common delivery system. In vivo prime-boost immunization using HIV-1 MPER-V3 could significantly enhance humoral and cellular immune responses as compared to control groups. The mixture of IgG1 and IgG2a was observed for each strategy, but IFN-γ production was significantly higher in prime-boost and peptide immunizations than that in DNA immunizations, inducing Th1 response. Moreover, our data showed that prime immunization with low dose of the nanoparticles (MPER-V3 DNA: MPG at ratio of 1:10) followed by MPER-V3 peptide drives T cell responses towards a Th1-type similar to high dose of the naked DNA prime/peptide boost immunization. Generally, the prime-boost strategy could improve both immune responses against MPER and especially V3 peptides suggesting its application as a promising HIV vaccine candidate in future.
开发一种有效的抗HIV-1感染疫苗是全球关注的主要问题。一种有效的HIV-1疫苗需要诱导和维持体液免疫和细胞免疫。在本研究中，使用MPER-V3注射，在DNA/DNA、肽/肽和DNA/肽（初免-加强）三种免疫策略中比较体液免疫和细胞免疫反应水平。MPG肽和Montanide 720分别用作DNA递送系统和肽佐剂。我们的结果表明，MPG在N/P比为10:1（~110-130nm）时与质粒DNA形成稳定的非共价纳米颗粒。使用MPG的MPER-V3 DNA的体外转染效率与作为常用递送系统的脂质体和TurboFect试剂相当。与对照组相比，使用HIV-1 MPER-V3进行体内初免-加强免疫可显著增强体液免疫和细胞免疫反应。每种策略均观察到IgG1和IgG2a的混合，但初免-加强免疫和肽免疫中的IFN-γ产生明显高于DNA免疫，诱导Th1反应。此外，我们的数据表明，用低剂量纳米颗粒（MPER-V3 DNA:MPG比例为1:10）进行初免，然后用MPER-V3肽激发，可使T细胞反应趋向于Th1型，类似于高剂量裸DNA初免/肽加强免疫。一般来说，初免-加强策略可以改善针对MPER尤其是V3肽的免疫反应，表明其在未来作为一种有前景的HIV疫苗候选物的应用价值。
