A recombinant protein vaccine induces protective immunity against SARS-CoV-2 JN.1 and XBB-lineage subvariants

被引：0

作者：

Yang, Jingyun ^{[1
]}

Hong, Weiqi ^{[1
]}

Shi, Huashan ^{[1
]}

Wang, Zhenling ^{[1
]}

He, Cai ^{[1
]}

Lei, Hong ^{[1
]}

Yan, Hong ^{[1
]}

Alu, Aqu ^{[1
]}

Ao, Danyi ^{[1
]}

Chen, Zimin ^{[1
]}

Zhou, Yanan ^{[2
]}

Yang, Hao ^{[2
]}

Yang, Yun ^{[2
]}

Yu, Wenhai ^{[2
]}

Tang, Cong ^{[2
]}

Wang, Junbin ^{[2
]}

Li, Bai ^{[2
]}

Huang, Qing ^{[2
]}

Hu, Hongbo ^{[1
]}

Cheng, Wei ^{[1
]}

Dong, Haohao ^{[1
]}

Lei, Jian ^{[1
]}

Chen, Lu ^{[1
]}

Zhou, Xikun ^{[1
]}

Yang, Li ^{[1
]}

Wang, Wei ^{[1
]}

Shen, Guobo ^{[1
]}

Yang, Jinliang ^{[1
]}

Zhao, Zhiwei ^{[1
]}

Song, Xiangrong ^{[1
]}

Sun, Qiangming ^{[2
]}

Wang, Youchun ^{[2
]}

Lu, Shuaiyao ^{[2
]}

Li, Jiong ^{[1
]}

Lu, Guangwen ^{[1
]}

Li, Weimin ^{[3
]}

Wei, Yuquan ^{[1
]}

Wei, Xiawei ^{[1
]}

机构：

[1] Sichuan Univ, State Key Lab Biotherapy & Canc Ctr, Lab Aging Res & Canc Drug Target, Natl Clin Res Ctr Geriatr,West China Hosp, Chengdu 610041, Peoples R China

[2] Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Biol, Natl Kunming High level Biosafety Primate Res Ctr, Kunming, Yunnan, Peoples R China

[3] Sichuan Univ, Frontiers Sci Ctr Dis Related Mol Network, Ctr Precis Med,Dept Resp & Crit Care Med,West Chin, Precis Med Key Lab Sichuan Prov,West China Hosp, Chengdu, Peoples R China

来源：

SIGNAL TRANSDUCTION AND TARGETED THERAPY | 2025年 / 10卷 / 01期

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

RESPONSES;

D O I：

10.1038/s41392-025-02154-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The emergence of XBB- and JN.1-lineages with remarkable immune evasion characteristics have led to rises in breakthrough infections within populations. In addition, the unfavorable impacts of immune imprinting, stemming from continuous exposure to antigens from circulated viruses, have been observed to incline immune response against earlier lineages, thereby declining the neutralization to newly emerged Omicron subvariants. In response to this, the advancement of next-generation vaccines against COVID-19 targeting components from new subvariants such as XBB-lineage is imperative. In the current study, a self-assembled trimeric recombinant protein (RBDXBB.1.5-HR) was generated by concatenating the sequences of the receptor binding domain (RBD) derived from XBB.1.5 with heptad-repeat 1 (HR1) and HR2 sequences from the spike S2 subunit. Adjuvanted-RBDXBB.1.5-HR induced robust humoral and cellular immune responses, characterized by elevated neutralization against JN.1-inculuded subvariants and a substantial population of antigen-specific T memory cells. Protective immunity conferred by RBDXBB.1.5-HR vaccine was preserved post-immunization, as evidenced by germinal center B (GC B) and T follicular helper (Tfh) responses, sustained neutralization potency, and an increase in memory B cells (MBCs) and long-lived plasma cells (LLPCs). The RBDXBB.1.5-HR vaccine showed a favorable boosting effect when administered heterologously after three doses of inactivated virus (IV) and mRNA vaccines. Significantly, it provided protection against live Omicron EG.5.1 viruses in vivo. The monovalent RBDXBB.1.5-HR vaccine showed favorable safety and immunogenicity, boosting neutralizing antibodies against JN.1- and XBB-lineage subvariants in individuals with prior COVID-19 vaccinations. These findings highlight its clinical potential in safeguarding against circulating Omicron subvariants.

引用

页数：15

共 52 条

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