The Interleukin-33-Group 2 Innate Lymphoid Cell Axis Represents a Potential Adjuvant Target To Increase the Cross-Protective Efficacy of Influenza Vaccine.
The Interleukin-33-Group 2 Innate Lymphoid Cell Axis Represents a Potential Adjuvant Target To Increase the Cross-Protective Efficacy of Influenza Vaccine.
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Interleukin-33-Group 2 先天淋巴细胞轴代表了提高流感疫苗交叉保护功效的潜在佐剂靶点。
DOI：
10.1128/jvi.00598-21
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发表时间：
2021
影响因子：
5.4
通讯作者：
Furuya,Yoichi
中科院分区：
文献类型：
--
作者：
Williams,ClareM;Roy,Sreeja;Califano,Danielle;McKenzie,AndrewNJ;Metzger,DennisW;Furuya,Yoichi
白细胞介素-33 （IL-33）是一种介导2型主导免疫反应的多功能细胞因子。相比之下，通常旨在诱导1型免疫的IL-33在病毒疫苗接种中的作用尚未得到充分研究。在这里，我们研究了IL-33对流感疫苗反应的影响。我们发现IL-33与灭活流感病毒疫苗鼻内共给药可提高疫苗抗流感病毒感染的效力，不仅适用于同源株，也适用于异源株，包括2009年H1N1流感病毒大流行株。交叉保护依赖于2组先天淋巴样细胞（ILC2s），因为在ILC2s缺陷的C57BL/ 6il7rre /+Rorafl/flmice中，IL-33对疫苗效力的有益作用被取消。此外，机制研究表明，il -33激活的ILC2s通过增强粘膜体液免疫，特别是IgA反应，可能以Th2细胞因子依赖的方式增强疫苗效力。我们的研究结果表明，il -33介导的ILC2s激活是一个关键的早期事件，对诱导粘膜体液免疫很重要，这反过来又负责对流感的跨株保护。因此，我们揭示了IL-33-ILC2轴在建立广泛保护性和持久的流感体液粘膜免疫中的作用，这一知识可能有助于开发通用流感疫苗。目前的流感疫苗虽然能够预防疫苗中包含的预测病毒/毒株，但无法提供针对新出现/新型毒株的交叉保护。因此，我们迫切需要一种能够预防多种流感病毒的通用疫苗。我们的新发现表明，涉及肺部ILC2s激活的粘膜疫苗接种策略在引发肺部交叉保护性体液免疫方面非常有效。这表明可以利用肺ILC2s的生物学特性来提高市售流感亚单位疫苗的交叉反应性。
Interleukin-33 (IL-33) is a multifunctional cytokine that mediates type 2-dominated immune responses. In contrast, the role of IL-33 during viral vaccination, which often aims to induce type 1 immunity, has not been fully investigated. Here, we examined the effects of IL-33 on influenza vaccine responses. We found that intranasal coadministration of IL-33 with an inactivated influenza virus vaccine increases vaccine efficacy against influenza virus infection, not only with the homologous strain but also with heterologous strains, including the 2009 H1N1 influenza virus pandemic strain. Cross-protection was dependent on group 2 innate lymphoid cells (ILC2s), as the beneficial effect of IL-33 on vaccine efficacy was abrogated in ILC2-deficient C57BL/6Il7rCre/+Rorafl/flmice. Furthermore, mechanistic studies revealed that IL-33-activated ILC2s potentiate vaccine efficacy by enhancing mucosal humoral immunity, particularly IgA responses, potentially in a Th2 cytokine-dependent manner. Our results demonstrate that IL-33-mediated activation of ILC2s is a critical early event that is important for the induction of mucosal humoral immunity, which in turn is responsible for cross-strain protection against influenza. Thus, we reveal a previously unrecognized role for the IL-33–ILC2 axis in establishing broadly protective and long-lasting humoral mucosal immunity against influenza, knowledge that may help in the development of a universal influenza vaccine.IMPORTANCECurrent influenza vaccines, although capable of protecting against predicted viruses/strains included in the vaccine, are inept at providing cross-protection against emerging/novel strains. Thus, we are in critical need of a universal vaccine that can protect against a wide range of influenza viruses. Our novel findings show that a mucosal vaccination strategy involving the activation of lung ILC2s is highly effective in eliciting cross-protective humoral immunity in the lungs. This suggests that the biology of lung ILC2s can be exploited to increase the cross-reactivity of commercially available influenza subunit vaccines.
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