a Emory Vaccine Center, Department of Microbiology and Immunology , Yerkes National Primate Research Center, Emory University , Atlanta , GA , USA.
Expert Rev Vaccines. 2017 Oct;16(10):973-985. doi: 10.1080/14760584.2017.1371594. Epub 2017 Sep 4.
Despite 30 years of research on HIV, a vaccine to prevent infection and limit disease progression remains elusive. The RV144 trial showed moderate, but significant protection in humans and highlighted the contribution of antibody responses directed against HIV envelope as an important immune correlate for protection. Efforts to further build upon the progress include the use of a heterologous prime-boost regimen using DNA as the priming agent and the attenuated vaccinia virus, Modified Vaccinia Ankara (MVA), as a boosting vector for generating protective HIV-specific immunity. Areas covered: In this review, we summarize the immunogenicity of DNA/MVA vaccines in non-human primate models and describe the efficacy seen in SIV infection models. We discuss immunological correlates of protection determined by these studies and potential approaches for improving the protective immunity. Additionally, we describe the current progress of DNA/MVA vaccines in human trials. Expert commentary: Efforts over the past decade have provided the opportunity to better understand the dynamics of vaccine-induced immune responses and immune correlates of protection against HIV. Based on what we have learned, we outline multiple areas where the field will likely focus on in the next five years.
尽管已经对 HIV 进行了 30 年的研究,但预防感染和限制疾病进展的疫苗仍然难以捉摸。RV144 试验在人类中显示出适度但显著的保护作用,并强调了针对 HIV 包膜的抗体反应作为保护的重要免疫相关性的贡献。进一步推进这一进展的努力包括使用异源初免-加强方案,使用 DNA 作为起始剂,以及使用减毒痘苗病毒,改良安卡拉痘苗(MVA)作为增强载体,以产生保护性的 HIV 特异性免疫。
涵盖领域:在这篇综述中,我们总结了 DNA/MVA 疫苗在非人类灵长类动物模型中的免疫原性,并描述了在 SIV 感染模型中观察到的疗效。我们讨论了这些研究确定的保护免疫的免疫学相关性,并探讨了提高保护性免疫的潜在方法。此外,我们还描述了 DNA/MVA 疫苗在人体试验中的最新进展。
专家评论:过去十年的努力使我们有机会更好地了解疫苗诱导的免疫反应和针对 HIV 的保护免疫相关性的动态。基于我们所学到的知识,我们概述了该领域在未来五年可能关注的多个领域。
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