Therapeutic vaccines against HIV infection
Therapeutic vaccines against HIV infection
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DOI：
10.4161/hv.19555
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发表时间：
2012-05-01
影响因子：
4.8
通讯作者：
Gallart, Teresa
中科院分区：
文献类型：
--
作者：
Garcia, Felipe;Leon, Agathe;Gallart, Teresa
对药物的耐药性、中长期的不良反应以及费用，都对终身坚持联合抗逆转录病毒疗法（cART）构成了重要限制。在此背景下，针对艾滋病病毒（HIV）感染患者终身使用cART的新治疗替代方案值得研究。一些数据表明，强大的T细胞介导的针对HIV的免疫反应确实能够限制病毒复制，并防止CD4细胞耗竭和疾病进展。有人提出将cART与免疫疗法相结合，以恢复和/或增强针对HIV的免疫特异性反应，最终目的是实现功能性治愈。在这种情况下，新的、诱导产生的针对HIV的特异性免疫反应将能够将病毒复制控制在检测不到的水平，类似于少数无需治疗就能控制病毒复制且不会发展为艾滋病的患者的情况。经典的方法，如全灭活病毒或重组蛋白，最初被证明可作为治疗性疫苗使用。然而，总体而言，这些早期疫苗增强针对HIV的特异性反应的能力非常有限，研究结果令人失望，因为没有显示出一致的免疫原性，对病毒载量也没有明显影响。近年来，基于更具创新性的载体，如DNA、重组病毒或树突状细胞，开发出了一些新方法。这些新载体的大多数临床试验已经证明它们能够诱导针对HIV的特异性免疫反应，尽管在控制病毒复制方面效果非常有限。然而，一些初步结果表明，基于树突状细胞的疫苗是最有希望的候选疫苗。为了提高这些疫苗的有效性，需要更好地了解保护机制、病毒学控制和免疫恶化情况；没有这些知识，有效的治疗性疫苗将仍然难以实现。
Resistance to medication, adverse effects in the medium-to-long-term and cost all place important limitations on lifelong adherence to combined antiretroviral therapy (cART). In this context, new therapeutic alternatives to cART for life in HIV-infected patients merit investigation. Some data suggest that strong T cell-mediated immunity to HIV can indeed limit virus replication and protect against CD4 depletion and disease progression. The combination of cART with immune therapy to restore and/or boost immune-specific responses to HIV has been proposed, the ultimate aim being to achieve a functional cure. In this scenario, new, induced, HIV-specific immune responses would be able to control viral replication to undetectable levels, mimicking the situation of the minority of patients who control viral replication without treatment and do not progress to AIDS. Classical approaches such as whole inactivated virus or recombinant protein initially proved useful as therapeutic vaccines. Overall, however, the ability of these early vaccines to increase HIV-specific responses was very limited and study results were discouraging, as no consistent immunogenicity was demonstrated and there was no clear impact on viral load. Recent years have seen the development of new approaches based on more innovative vectors such as DNA, recombinant virus or dendritic cells. Most clinical trials of these new vectors have demonstrated their ability to induce HIV-specific immune responses, although they show very limited efficacy in terms of controlling viral replication. However, some preliminary results suggest that dendritic cell-based vaccines are the most promising candidates. To improve the effectiveness of these vaccines, a better understanding of the mechanisms of protection, virological control and immune deterioration is required; without this knowledge, an efficacious therapeutic vaccine will remain elusive.