一种启动或增强人抗原特异性CD8 T细胞反应的体外方法:在疫苗研究中的应用。

An In Vitro Approach to Prime or Boost Human Antigen-Specific CD8 T Cell Responses: Applications to Vaccine Studies.

作者信息

Nguyen Hoang Oanh, Cabral-Piccin Mariela P, Appay Victor, Papagno Laura

机构信息

Univ. Bordeaux, CNRS, Inserm, ImmunoConcEpT, UMR 5164, ERL 1303, F-33000 Bordeaux, France.

International Research Center, A.C.Camargo Cancer Center, São Paulo 01508-010, Brazil.

出版信息

Vaccines (Basel). 2025 Jul 4;13(7):729. doi: 10.3390/vaccines13070729.

Abstract

Although vaccine development has primarily focused on inducing neutralizing antibodies, increasing evidence supports an important role of CD8 T cell responses in vaccine effectiveness. Routine assays, which are mainly based on antibody titers, may therefore not accurately reflect the full immune response elicited by vaccination. Assessing antigen-specific T cell responses upon vaccination poses several challenges. A common issue in studying T cells specific to a vaccine antigen is their low frequency in circulation, which can limit their ex vivo analysis. Moreover, the use of human cell-based models is crucial for studying and optimizing the induction of T cell responses to design effective vaccines. We developed an innovative in vitro approach of human CD8 T cell priming, based on the rapid mobilization of dendritic cells (DCs) directly from unfractionated peripheral blood mononuclear cells (PBMCs). This simple and original method allows for side-by-side comparisons of multiple test parameters in a standardized system, providing both quantitative and qualitative readouts of primed antigen-specific CD8 T cells. Here, we discuss the genesis of this approach and its versatile applications, including monitoring antigen-specific T cell responses, evaluating an individual's T cell priming capacity, and conducting preclinical studies on potential adjuvants and vaccine candidates.

摘要

尽管疫苗研发主要集中在诱导中和抗体,但越来越多的证据支持CD8 T细胞反应在疫苗有效性中发挥重要作用。因此,主要基于抗体滴度的常规检测可能无法准确反映疫苗接种引发的完整免疫反应。评估疫苗接种后的抗原特异性T细胞反应面临诸多挑战。研究疫苗抗原特异性T细胞的一个常见问题是它们在循环中的频率较低,这可能会限制其体外分析。此外,使用基于人类细胞的模型对于研究和优化T细胞反应的诱导以设计有效的疫苗至关重要。我们基于从未经分离的外周血单核细胞(PBMC)中直接快速动员树突状细胞(DC),开发了一种创新的体外人类CD8 T细胞致敏方法。这种简单且独特的方法允许在标准化系统中对多个测试参数进行并行比较,提供致敏抗原特异性CD8 T细胞的定量和定性读数。在此,我们讨论这种方法的起源及其广泛应用,包括监测抗原特异性T细胞反应、评估个体的T细胞致敏能力以及对潜在佐剂和候选疫苗进行临床前研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/496f/12300369/eadd843031ae/vaccines-13-00729-g001.jpg

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