A quadrivalent norovirus vaccine based on a chimpanzee adenovirus vector induces potent immunity in mice

Yihua Jiang; Lingjin Sun; Nan Qiao; Xiang Wang; Caihong Zhu; Man Xing; Hui Liu; Ping Zhou; Dongming Zhou

doi:10.1016/j.virs.2024.07.002

August 2024

Yihua Jiang, Lingjin Sun, Nan Qiao, Xiang Wang, Caihong Zhu, Man Xing, Hui Liu, Ping Zhou and Dongming Zhou. A quadrivalent norovirus vaccine based on a chimpanzee adenovirus vector induces potent immunity in mice[J]. Virologica Sinica, 2024, 39(4): 675-684. doi: 10.1016/j.virs.2024.07.002

Citation: Yihua Jiang, Lingjin Sun, Nan Qiao, Xiang Wang, Caihong Zhu, Man Xing, Hui Liu, Ping Zhou, Dongming Zhou. A quadrivalent norovirus vaccine based on a chimpanzee adenovirus vector induces potent immunity in mice .VIROLOGICA SINICA, 2024, 39(4) : 675-684. http://dx.doi.org/10.1016/j.virs.2024.07.002

基于黑猩猩腺病毒载体的四价诺如病毒疫苗可诱导小鼠产生强效免疫力

江易桦 ^a ,
孙羚津 ^a ,
乔楠 ^a ,
王祥 ^b ,
朱彩虹 ^b ,
邢嫚 ^a,b ,
刘辉 ^c,, ,
周萍 ^a,d,, ,
周东明 ^a,b,,

cstr: 32224.14.j.virs.2024.07.002

a. 天津医科大学基础医学院;
b. 复旦大学附属上海市公共卫生临床中心;
c. 成都康华生物制品有限公司研发中心;
d. 中国科学院上海免疫与感染研究所

通讯作者： 刘辉, liuhui@kangh.com; 周萍, 17317825924@163.com; 周东明, zhoudongming@tmu.edu.cn
收稿日期： 2023-11-20
录用日期： 2024-07-08

摘要

诺如病毒（NoV）感染是造成全球肠胃炎的主要病因。由于其基因和抗原的多样性，该病毒给开发具有广泛免疫保护作用的疫苗带来了巨大挑战。迄今为止，还没有获准用于临床的 NoV 疫苗。在此，我们以黑猩猩腺病毒 AdC68 为载体，开发了一种广谱的四价 NoV 疫苗，该载体携带诺如病毒 GI 和 GII 亚群的主要衣壳蛋白（VP1）。与肌肉注射（i.m.）、鼻内注射（i.n.）或其他初免-加强免疫方案（i.m. + i.m.、i.m. + i.n.、i.n. + i.m.）相比，AdC68-GI.1-GII.3 (E1)-GII.4-GII.17 (E3) 通过 i.n. + i.n.给药可诱导小鼠产生更高滴度的血清 IgG 抗体以及支气管肺泡灌洗液（BALF）和唾液中针对四种同源 VP1 的IgA 抗体，还能明显刺激产生针对四种基因型的阻断抗体。在病毒样颗粒（VLP）-GI.1、VLP-GII.3、VLP-GII.4 和 VLP-GII.17 的再次刺激下， i.n. + i.n. 策略接种的四价疫苗有效地引发了以 IFN-γ 分泌为主要特征的特异性T细胞免疫反应。此外，该新型四价 NoV 疫苗只需要制备一种重组腺病毒，就能针对主要的 GI/GII 流行株提供广泛的预防性免疫，因此是一种很有希望进一步开发的候选疫苗。
- 诺如病毒(NoV)
- , 四价疫苗
- , 腺病毒载体

A quadrivalent norovirus vaccine based on a chimpanzee adenovirus vector induces potent immunity in mice

Yihua Jiang ^a ,
Lingjin Sun ^a ,
Nan Qiao ^a ,
Xiang Wang ^b ,
Caihong Zhu ^b ,
Man Xing ^a,b ,
Hui Liu ^c,, ,
Ping Zhou ^a,d,, ,
Dongming Zhou ^a,b,,

a. Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China;
b. Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China;
c. R&D Centre, Chengdu Kanghua Biological Products Co., Ltd, Chengdu, 610000, China;
d. Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China

Corresponding author: Hui Liu, liuhui@kangh.com Ping Zhou, 17317825924@163.com Dongming Zhou, zhoudongming@tmu.edu.cn
Received Date: 20 November 2023
Accepted Date: 08 July 2024

Abstract

Norovirus (NoV) infection is a major cause of gastroenteritis worldwide. The virus poses great challenges in developing vaccines with broad immune protection due to its genetic and antigenic diversity. To date, there are no approved NoV vaccines for clinical use. Here, we aimed to develop a broad-acting quadrivalent NoV vaccine based on a chimpanzee adenovirus vector, AdC68, carrying the major capsid protein (VP1) of noroviral GI and GII genotypes. Compared to intramuscular (i.m.), intranasal (i.n.), or other prime-boost immunization regimens (i.m. + i.m., i.m. + i.n., i.n. + i.m.), AdC68-GI.1-GII.3 (E1)-GII.4-GII.17 (E3), administered via i.n. + i.n. induced higher titers of serum IgG antibodies and higher IgA antibodies in bronchoalveolar lavage fluid (BALF) and saliva against the four homologous VP1s in mice. It also significantly stimulated the production of blocking antibodies against the four genotypes. In response to re-stimulation with virus-like particles (VLP)-GI.1, VLP-GII.3, VLP-GII.4, and VLP-GII.17, the quadrivalent vaccine administered according to the i.n. + i.n. regimen effectively triggered specific cell-mediated immune responses, primarily characterized by IFN-γ secretion. Furthermore, the preparation of this novel quadrivalent NoV vaccine requires only a single recombinant adenovirus to provide broad preventive immunity against the major GI/GII epidemic strains, making it a promising vaccine candidate for further development.
- Norovirus (NoV)
- , Quadrivalent vaccine
- , Adenovirus vector

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