A safe and effective mucosal RSV vaccine in mice consisting of RSV phosphoprotein and flagellin variant

被引：23

作者：

Zhao, Bali ^{[1
,2
]}

Yang, Jingyi ^{[1
,2
]}

He, Bing ^{[3
]}

Li, Xian ^{[2
]}

Yan, Hu ^{[2
]}

Liu, Shuning ^{[3
]}

Yang, Yi ^{[2
]}

Zhou, Dihan ^{[2
]}

Liu, Bowen ^{[2
]}

Fan, Xuxu ^{[2
]}

Zhong, Maohua ^{[2
,4
]}

Zhang, Ejuan ^{[2
,5
]}

Zhang, Fan ^{[6
]}

Zhang, Yue ^{[2
]}

Chen, Yao-Qing ^{[3
]}

Jiang, Shibo ^{[1
,7
]}

Yan, Huimin ^{[1
,2
]}

机构：

[1] Fudan Univ, Vaccine & Immunol Res Ctr, Shanghai Publ Hlth Clin Ctr, Translat Med Res Inst, Shanghai 201508, Peoples R China

[2] Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Mucosal Immun Res Grp, Wuhan 430071, Peoples R China

[3] Sun Yat Sen Univ, Sch Publ Hlth Shenzhen, Shenzhen 518107, Peoples R China

[4] Wuhan Univ Sci & Technol, Med Coll, Inst Infect, Hubei Prov Key Lab Occupat Hazard Identificat & C, Wuhan 430065, Peoples R China

[5] Wuhan Univ, Med Sci Res Ctr, Zhongnan Hosp, Wuhan 430071, Peoples R China

[6] Chinese Acad Sci, Wuhan Inst Virol, Core Facil & Tech Support, Wuhan 430071, Peoples R China

[7] Fudan Univ, Shanghai Med Coll, Sch Basic Med Sci, Key Lab Med Mol Virol,MOE,NHC,CAMS, Shanghai 200032, Peoples R China

来源：

CELL REPORTS | 2021年 / 36卷 / 03期

基金：

中国国家自然科学基金;

关键词：

RESPIRATORY-SYNCYTIAL-VIRUS; PAC FUSION PROTEIN; CD4; T-CELLS; INFLAMMATORY RESPONSE; ESCHERICHIA-COLI; VIRAL-INFECTION; INFLUENZA; PROTECTION; CHILDREN; IMMUNITY;

D O I：

10.1016/j.celrep.2021.109401

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Respiratory syncytial virus (RSV) is a major cause of serious acute lower respiratory tract infection in infants and the elderly. The lack of a licensed RSV vaccine calls for the development of vaccines with other targets and vaccination strategies. Here, we construct a recombinant protein, designated P-KFD1, comprising RSV phosphoprotein (P) and the E.-coli-K12-strain-derived flagellin variant KFD1. Intranasal immunization with P-KFD1 inhibits RSV replication in the upper and lower respiratory tract and protects mice against lung disease without vaccine-enhanced disease (VED). The P-specific CD4(+) T cells provoked by P-KFD1 intranasal (i.n.) immunization either reside in or migrate to the respiratory tract and mediate protection against RSV infection. Single-cell RNA sequencing (scRNA-seq) and carboxyfluorescein succinimidyl ester (CFSE)-labeled cell transfer further characterize the Th1 and Th17 responses induced by P-KFD1. Finally, we find that anti-viral protection depends on either interferon-gamma (IFN-gamma) or interleukin-17A (IL-17A). Collectively, P-KFD1 is a promising safe and effective mucosal vaccine candidate for the prevention of RSV infection.

引用

页数：22