HIV-1 bNAb疫苗效果——未达到的目标?

IF 1 4区 医学 Q4 IMMUNOLOGY
Hannah King, Mario Roederer, Diane L Bolton
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引用次数: 0

摘要

有报道称hiv -1特异性宽中和单克隆抗体(bNAbs)介导潜在的“疫苗效应”,暗示被动转移的bNAbs促进内源性抗hiv -1免疫应答。迄今为止,有三个临床试验报告,在给HIV感染者服用bNAb后,抗HIV-1中和抗体或T细胞反应增加。尽管人们对这一假说有着强烈的热情,很大程度上是由于它在HIV-1治疗策略中的潜在应用,但疫苗效应的机制仍不清楚。此外,疫苗对抗体和T细胞反应的影响并不一致。在一定程度上,这种不一致可能是由于在人体临床试验的背景下,在敏感地测量疫苗效果方面存在许多困难。服用bNAb后,免疫反应的增加幅度通常是适度的,即使在观察到这种情况时也是如此;中和或T细胞反应可能需要更大程度的增强才能产生生物学上有意义的影响。我们回顾了评估HIV-1/SIV单克隆抗体疫苗效应的临床和临床前非人灵长类动物研究,重点介绍了这些研究的优势和局限性。讨论了未来研究调查疫苗效应的考虑因素,包括适当的比较物和特异性控制。最后,精英对照队列的免疫应答特征被概述为更有可能介导HIV-1抑制的潜在疫苗效应终点。随着bNAb治疗干预越来越多地转向联合方法,包括结合免疫调节剂,关注纳入适当对照组的研究设计,以及相关的免疫原性分析,将能够更结论性地解释可能介导持久控制HIV的疫苗效果。无论如何,迄今为止,疫苗效应的产生令人失望。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
HIV-1 bNAb Vaccinal Effect - An Underachieving Goal?

Reports of HIV-1-specific broadly neutralizing monoclonal antibodies (bNAbs) medi-ating a potential 'vaccinal effect' implicate passively transferred bNAbs in promoting endoge-nous anti-HIV-1 immune responses. To date, three clinical trials have reported either increased anti-HIV-1 neutralizing antibodies or T cell responses following bNAb administration to people living with HIV. Despite strong enthusiasm for this hypothesis, motivated in large part by its potential application to HIV-1 therapeutic strategies, the mechanism(s) underlying a vaccinal ef-fect remain unclear. Moreover, vaccinal effects on antibody and T cell responses are not consist-ently replicated. Partly, this inconsistency may be due to numerous difficulties in sensitively measuring a vaccinal effect in the context of human clinical trials. The magnitude of immune response increase following bNAb administration is generally modest, even when it is observed; a far greater enhancement of neutralization or T cell responses is likely required for a biologically meaningful impact. We review clinical and pre-clinical nonhuman primate studies that evaluated HIV-1/SIV monoclonal antibodies for vaccinal effects, with an emphasis on the strengths and limitations of these studies. Considerations for future studies investigating vaccinal effects are discussed, including appropriate comparators and specificity controls. Lastly, immune response characteristics of elite controller cohorts are outlined as potential vaccinal effect endpoints more likely to mediate HIV-1 suppression. As bNAb therapeutic interventions increasingly turn to combination approaches, including incorporation of immunomodulatory agents, attention to study design incorporating appropriate control groups, and relevant immunogenicity assays will enable more conclusive interpretation of vaccinal effects likely to mediate durable control of HIV. In any case, to date, the elicitation of vaccinal effects has been disappointing.

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来源期刊
Current HIV Research
Current HIV Research 医学-病毒学
CiteScore
1.90
自引率
10.00%
发文量
81
审稿时长
6-12 weeks
期刊介绍: Current HIV Research covers all the latest and outstanding developments of HIV research by publishing original research, review articles and guest edited thematic issues. The novel pioneering work in the basic and clinical fields on all areas of HIV research covers: virus replication and gene expression, HIV assembly, virus-cell interaction, viral pathogenesis, epidemiology and transmission, anti-retroviral therapy and adherence, drug discovery, the latest developments in HIV/AIDS vaccines and animal models, mechanisms and interactions with AIDS related diseases, social and public health issues related to HIV disease, and prevention of viral infection. Periodically, the journal invites guest editors to devote an issue on a particular area of HIV research of great interest that increases our understanding of the virus and its complex interaction with the host.
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