Ide Fuyuaki, Nakamura Tetsuya, Tomizawa Mariko, Kawana-Tachikawa Ai, Odawara Takashi, Hosoya Noriaki, Iwamoto Aikichi
Department of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
J Med Virol. 2006 Jun;78(6):711-8. doi: 10.1002/jmv.20612.
Immune response enhanced by therapeutic HIV-1 vaccine may control viral proliferation after discontinuation of highly active antiretroviral therapy (HAART). Although which strategies for therapeutic vaccination are feasible remains controversial, application of dendritic cells (DCs) as a vaccine adjuvant represents a promising approach to improving deteriorated immune function in HIV-1-infected individuals. The safety and efficacy of DC-based vaccine loaded with HIV-1-derived cytotoxic T lymphocytes (CTL) peptides were thus investigated in this study. Autologous DCs loaded with seven CTL peptides with HLA-A*2402 restriction were immunized to four HIV-1-infected individuals under HAART. In terms of safety, peptide-loaded DCs were well tolerated, and only mild local and general symptoms were observed during vaccine administration. ELISPOT assays to detect IFN-gamma production in CD8(+) lymphocytes revealed a limited breadth of responses to immunized peptides in two of four participants, but no response in the remaining two participants. Differences in immunological response might be attributable to the fact that responders displayed higher nadir CD4 counts before starting HAART and were immunized with a larger number of DCs per reactive peptide than non-responders. Discontinuation of HAART after vaccination failed to lower viral set points compared to those before starting HAART. This early outcome warrants further exploration to elucidate the therapeutic value of vaccination with DCs in HIV-1 infection.
治疗性HIV-1疫苗增强的免疫反应可能在高效抗逆转录病毒疗法（HAART）中断后控制病毒增殖。尽管哪种治疗性疫苗接种策略可行仍存在争议，但应用树突状细胞（DCs）作为疫苗佐剂是改善HIV-1感染个体恶化的免疫功能的一种有前景的方法。因此，本研究对负载HIV-1来源的细胞毒性T淋巴细胞（CTL）肽的基于DC的疫苗的安全性和有效性进行了研究。将负载有七种具有HLA-A*2402限制性的CTL肽的自体DCs接种给四名接受HAART的HIV-1感染个体。在安全性方面，负载肽的DCs耐受性良好，在疫苗接种期间仅观察到轻微的局部和全身症状。检测CD8(+)淋巴细胞中IFN-γ产生的ELISPOT分析显示，四名参与者中有两名对免疫肽的反应范围有限，而其余两名参与者无反应。免疫反应的差异可能归因于以下事实：有反应者在开始HAART之前的最低点CD4计数较高，并且每反应性肽接种的DC数量比无反应者多。与开始HAART之前相比，疫苗接种后中断HAART未能降低病毒载量。这一早期结果值得进一步探索，以阐明用DCs接种疫苗在HIV-1感染中的治疗价值。
