A unique nanoparticulate TLR9 agonist enables a HA split vaccine to confer FcγR-mediated protection against heterologous lethal influenza virus infection
A unique nanoparticulate TLR9 agonist enables a HA split vaccine to confer FcγR-mediated protection against heterologous lethal influenza virus infection
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独特的纳米颗粒 TLR9 激动剂使 HA 裂解疫苗能够赋予 FcγR 介导的针对异源致死性流感病毒感染的保护作用
DOI：
10.1093/intimm/dxy069
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发表时间：
2018
影响因子：
4.4
通讯作者：
Ishii Ken J
中科院分区：
文献类型：
--
作者：
Yamamoto Takuya;Masuta Yuji;Momota Masatoshi;Kanekiyo Masaru;Kanuma Tomohiro;Takahama Shoukichi;Moriishi Eiko;Yasutomi Yasuhiro;Saito Takashi;Graham Barney S;Takahashi Yoshimasa;Ishii Ken J
开发一种能够针对更广泛的流感病毒株提供强大和持久保护的通用流感疫苗是全球公共卫生的优先事项。提高疫苗效力的一种方法是使用佐剂来增强对靶抗原的免疫应答;然而，佐剂在流感疫苗背景下的作用尚未完全理解。我们先前已经开发了K3-葡聚糖（SPG）佐剂，其由纳米颗粒化的寡脱氧核苷酸K3（一种TLR 9激动剂）和SPG（一种Dectin-1的非激动性β-葡聚糖配体）组成。在这项研究中，K3-SPG与常规流感血凝素（HA）裂解疫苗（K3-SPG HA）一起给予，可提供针对抗原错配异源病毒攻击的保护。虽然K3-SPG HA引起了稳健的交叉反应性HA特异性IgG 2c和CD 8 T细胞应答，但CD 8 T细胞耗竭对这种交叉保护没有影响。相反，K3-SPG HA不能在FcRγ缺陷小鼠中赋予针对异源病毒攻击的保护。我们的结果表明，由HA抗原和K3-SPG佐剂诱导的Fcγ R介导的抗体应答对于有效保护免受抗原错配的流感病毒感染是重要的。因此，我们证明了K3-SPG佐剂疫苗策略扩大了针对流感的保护性免疫，并为下一代流感疫苗的开发提供了基础。
The development of a universal influenza vaccine that can provide a robust and long-lasting protection against a broader range of influenza virus strains is a global public health priority. One approach to improve vaccine efficacy is to use an adjuvant to boost immune responses to the target antigens; nevertheless, the role of adjuvants in the context of influenza vaccines is not fully understood. We have previously developed the K3-schizophyllan (SPG) adjuvant, which is composed of nanoparticulated oligodeoxynucleotides K3, a TLR9 agonist, with SPG, a non-agonistic β-glucan ligand of Dectin-1. In this study, K3-SPG given with conventional influenza hemagglutinin (HA) split vaccine (K3-SPG HA) conferred protection against antigenically mismatched heterologous virus challenge. While K3-SPG HA elicited robust cross-reactive HA-specific IgG2c and CD8 T-cell responses, CD8 T-cell depletion had no impact on this cross-protection. In contrast, K3-SPG HA was not able to confer protection against heterologous virus challenge in FcRγ-deficient mice. Our results indicated that FcγR-mediated antibody responses induced by the HA antigen and K3-SPG adjuvant were important for potent protection against antigenically mismatched influenza virus infection. Thus, we demonstrated that the K3-SPG-adjuvanted vaccine strategy broadens protective immunity against influenza and provides a basis for the development of next-generation influenza vaccines.