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

IF 4.5 3区 医学 Q2 IMMUNOLOGY Current Opinion in HIV and AIDS Pub Date : 2023-11-01 Epub Date: 2023-09-11 DOI:10.1097/COH.0000000000000819
James A Counts, Kevin O Saunders
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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.

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指导临床前非人灵长类动物研究的HIV-1疫苗开发。
综述的目的:在解剖学和免疫系统组成方面,非人类灵长类动物(NHP)被视为最接近人类的动物模型。在这里,我们回顾了该模型系统中的临床前研究如何教授HIV疫苗学领域通过疫苗接种诱导广泛中和抗体(bnAbs)并引发保护性T细胞反应所需的基本免疫学。这些经验教训正在转化为临床试验,以推进针对HIV-1感染的保护性主动疫苗接种。最近的发现:NHP的临床前疫苗接种研究表明,高度工程化的HIV-1免疫原可以启动bnAb前体,为I期临床试验提供了概念证明。此外,HIV-1感染的NHP模型正在阐明bnAb发展的途径,同时作为评估疫苗保护性的系统。创新的免疫策略提高了HIV-1抗体在长寿生发中心的亲和力成熟度。猕猴的临床前研究已经确定了中和抗体的保护水平,并表明T细胞反应可以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,作为临床试验的基准,加速了HIV疫苗的设计。
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来源期刊
Current Opinion in HIV and AIDS
Current Opinion in HIV and AIDS IMMUNOLOGY-INFECTIOUS DISEASES
CiteScore
7.40
自引率
7.30%
发文量
115
审稿时长
6-12 weeks
期刊介绍: Published bimonthly and offering a unique and wide ranging perspective on the key developments in the field, each issue of Current Opinion in HIV and AIDS features hand-picked review articles from our team of expert editors. With six disciplines published across the year – including HIV and ageing, a HIV vaccine, and epidemiology – every issue also contains annotated reference detailing the merits of the most important papers.
期刊最新文献
Recent data on the role of antiretroviral therapy in weight gain and obesity in persons living with HIV. Anticipating HIV viral escape - resistance to active and passive immunization. Accelerating HIV vaccine development through meaningful engagement of local scientists and communities. Guiding HIV-1 vaccine development with preclinical nonhuman primate research. Discovery medicine - the HVTN's iterative approach to developing an HIV-1 broadly neutralizing vaccine.
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