Hospital Clinic-HIVACAT, IDIBAPS, University of Barcelona, Barcelona, Spain.
Hum Vaccin Immunother. 2012 May;8(5):569-81. doi: 10.4161/hv.19555. Epub 2012 May 1.
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.
抗药性、中长期不良反应和成本都对艾滋病毒感染者终身坚持联合抗逆转录病毒疗法（cART）造成了重要限制。在这种情况下，有必要研究艾滋病毒感染者的新治疗选择，以替代“终生接受 cART”。一些数据表明，艾滋病毒的强烈 T 细胞介导免疫确实可以限制病毒复制，防止 CD4 细胞耗竭和疾病进展。已经提出了将 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，最终目标是实现“功能性治愈”。在这种情况下，新的、诱导的、针对 HIV 的免疫反应将能够将病毒复制控制在无法检测的水平，类似于少数能够在不治疗的情况下控制病毒复制且不会进展为艾滋病的患者的情况。经典方法，如全灭活病毒或重组蛋白，最初被证明是有用的治疗性疫苗。然而，总的来说，这些早期疫苗增加 HIV 特异性反应的能力非常有限，研究结果令人沮丧，因为没有证明其具有一致性的免疫原性，也没有对病毒载量产生明显影响。近年来，出现了基于更具创新性载体的新方法，如 DNA、重组病毒或树突状细胞。这些新载体的大多数临床试验都证明了它们能够诱导 HIV 特异性免疫反应，尽管它们在控制病毒复制方面的疗效非常有限。然而，一些初步结果表明，基于树突状细胞的疫苗是最有前途的候选者。为了提高这些疫苗的有效性，需要更好地了解保护、病毒学控制和免疫恶化的机制；没有这些知识，有效的治疗性疫苗仍将难以实现。
