Development of T follicular helper cell-independent nanoparticle vaccines for SARS-CoV-2 or HIV-1 by targeting ICOSL.

IF 6.9 1区 医学 Q1 IMMUNOLOGY NPJ Vaccines Pub Date : 2024-09-28 DOI:10.1038/s41541-024-00971-4
Yongli Zhang, Achun Chen, Daiying Li, Quyu Yuan, Airu Zhu, Jieyi Deng, Yalin Wang, Jie Liu, Chaofeng Liang, Wenjie Li, Qiannan Fang, Jiatong Xie, Xiantao Zhang, Xu Zhang, Yiwen Zhang, Ran Chen, Ting Pan, Hui Zhang, Xin He
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Abstract

T helper cells, particularly T follicular helper (TFH) cells, are essential for the neutralizing antibody production elicited by pathogens or vaccines. However, in immunocompromised individuals, the inefficient support from TFH cells could lead to limited protection after vaccine inoculation. Here we showed that the conjugation of inducible T cell costimulatory (ICOS) onto the nanoparticle, together with immunogen, significantly enhanced the immune response of the vaccines specific for SARS-CoV-2 or human immunodeficiency virus type-1 (HIV-1) in TFH-deficient mice. Further studies indicated that ICOSL on B cells was triggered by ICOS binding, subsequently activated the PKCβ signaling pathway, and enhanced the survival and proliferation of B cells. Our findings revealed that the stimulation of ICOS-ICOSL interaction by adding ICOS on the nanoparticle vaccine significantly substitutes the function of TFH cells to support B cell response, which is significant for the immunocompromised people, such as the elderly or HIV-1-infected individuals.

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以 ICOSL 为靶点,开发不依赖 T 滤泡辅助细胞的纳米颗粒疫苗,用于治疗 SARS-CoV-2 或 HIV-1。
T辅助细胞,尤其是T滤泡辅助细胞(TFH),对于病原体或疫苗引起的中和抗体的产生至关重要。然而,在免疫力低下的个体中,TFH 细胞的低效支持可能会导致疫苗接种后的保护效果有限。在这里,我们发现在纳米颗粒上连接诱导性 T 细胞刺激因子(ICOS)和免疫原,能显著增强 TFH 缺陷小鼠对 SARS-CoV-2 或人类免疫缺陷病毒 1 型(HIV-1)特异性疫苗的免疫反应。进一步的研究表明,B 细胞上的 ICOSL 是由 ICOS 结合触发的,随后激活了 PKCβ 信号通路,并增强了 B 细胞的存活和增殖。我们的研究结果表明,在纳米颗粒疫苗中添加 ICOS 可刺激 ICOS-ICOSL 相互作用,从而显著替代 TFH 细胞支持 B 细胞应答的功能,这对免疫功能低下的人群(如老年人或 HIV-1 感染者)意义重大。
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来源期刊
NPJ Vaccines
NPJ Vaccines Immunology and Microbiology-Immunology
CiteScore
11.90
自引率
4.30%
发文量
146
审稿时长
11 weeks
期刊介绍: Online-only and open access, npj Vaccines is dedicated to highlighting the most important scientific advances in vaccine research and development.
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