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利用临床前非人灵长类动物研究指导HIV-1疫苗的开发。

Guiding HIV-1 vaccine development with preclinical nonhuman primate research.

作者信息

Counts James A, Saunders Kevin O

机构信息

Duke Human Vaccine Institute, Department of Medicine.

Duke Human Vaccine Institute, Departments of Surgery, Immunology, and Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA.

出版信息

Curr Opin HIV AIDS. 2023 Nov 1;18(6):315-322. doi: 10.1097/COH.0000000000000819. Epub 2023 Sep 11.

Abstract

PURPOSE OF THE REVIEW

Nonhuman primates (NHPs) are seen as the closest animal model to humans in terms of anatomy and immune system makeup. Here, we review how preclinical studies in this model system are teaching the field of HIV vaccinology the basic immunology that is needed to induce broadly neutralizing antibodies (bnAbs) with vaccination and elicit protective T cell responses. These lessons are being translated into clinical trials to advance towards protective active vaccination against HIV-1 infection.

RECENT FINDINGS

Preclinical vaccination studies in NHPs have shown that highly engineered HIV-1 immunogens can initiate bnAb precursors providing proof of concept for Phase I clinical trials. Additionally, NHP models of HIV-1 infection are elucidating the pathways for bnAb development while serving as systems to evaluate vaccine protection. Innovative immunization strategies have increased affinity maturation of HIV-1 antibodies in long-lived germinal centers. Preclinical studies in macaques have defined the protective level of neutralizing antibodies and have shown that T cell responses can synergize with antibody-mediated immunity to provide protection in the presence of lower neutralizing antibody titers.

SUMMARY

The NHP model provides vaccine regimens and desired antibody and T cell responses that serve as benchmarks for clinical trials, accelerating HIV vaccine design.

摘要

综述目的

就解剖结构和免疫系统组成而言,非人灵长类动物(NHPs)被视为与人类最接近的动物模型。在此,我们综述在该模型系统中进行的临床前研究如何向HIV疫苗学领域传授通过疫苗接种诱导广泛中和抗体(bnAbs)并引发保护性T细胞反应所需的基础免疫学知识。这些经验教训正被转化为临床试验,以推动针对HIV-1感染的保护性主动疫苗接种取得进展。

最新发现

在NHPs中进行的临床前疫苗接种研究表明,高度工程化的HIV-1免疫原可启动bnAb前体,为I期临床试验提供概念验证。此外,HIV-1感染的NHP模型在阐明bnAb产生途径的同时,还可作为评估疫苗保护作用的系统。创新的免疫策略提高了长寿命生发中心中HIV-1抗体的亲和力成熟度。猕猴的临床前研究确定了中和抗体的保护水平,并表明T细胞反应可与抗体介导的免疫协同作用,在中和抗体滴度较低的情况下提供保护。

总结

NHP模型提供了疫苗方案以及所需的抗体和T细胞反应,这些可作为临床试验的基准,加速HIV疫苗的设计。

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