Respiratory syncytial virus F and G protein core fragments fused to HBsAg-binding protein (SBP) induce a Th1-dominant immune response without vaccine-enhanced disease

被引:5
作者
Khan, Inam Ullah [1 ]
Ahmad, Farooq [2 ,3 ]
Zhang, Shuren [4 ,5 ]
Lu, Panpan [1 ]
Wang, Jingbo [1 ]
Xie, Jun [1 ]
Zhu, Naishuo [1 ]
机构
[1] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Lab Mol Immunol, Shanghai 200433, Peoples R China
[2] Shanghai Jiao Tong Univ, State Key Lab Met Matrix Composites, 800 Dong Chuan Rd, Shanghai 200240, Peoples R China
[3] Shanghai Jiao Tong Univ, Shanghai Ctr Syst Biomed, 800 Dong Chuan Rd, Shanghai 200240, Peoples R China
[4] Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol, Minist Hlth, Shanghai 201508, Peoples R China
[5] Fudan Univ, Shanghai Med Coll, Minist Educ, Shanghai 201508, Peoples R China
基金
中国国家自然科学基金;
关键词
eosinophilia; RSV vaccine; T(h)1 response; VED; CONSERVED DOMAIN; G-GLYCOPROTEIN; RSV; INFECTION; PROTECTION; IMMUNIZATION; EOSINOPHILIA; ANTIBODIES; EPITOPES; STRATEGY;
D O I
10.1093/intimm/dxy078
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The induction of a dominant T(h)2-type response is the main cause of harmful inflammation in respiratory syncytial virus (RSV) vaccine trials. A balanced T(h)1 versus T(h)2 immune response is needed for a safe and effective RSV vaccine. In this study, we evaluated the potential of a recombinant protein SBP-FG as a vaccine candidate with the main focus on shifting the harmful T(h)2 response to a T(h)1 response. SBP-FG consists of epitopes from RSV fusion (F) and attachment (G) proteins conjugated to the N-terminus of HBsAg-binding protein (SBP). SBP-FG induced significantly stronger immune responses assessed at the level of total IgG, IgA and neutralizing antibodies as compared with formalin-inactivated RSV (FI-RSV) and live RSV. Analysis of IgG isotypes, lung cytokines and T helper cells showed that SBP-FG induced a dominant T(h)1-type response. Further, SBP-FG immunized mice showed significantly reduced lung eosinophilia, reduced viral multiplication in lungs after challenge infection and provided protection against RSV infection. These results suggest that SBP-FG can be developed into a safe and effective vaccine against RSV. However, more studies are required to further evaluate SBP-FG as a potent vaccine candidate against RSV. An effective RSV vaccine that does not trigger lung inflammation
引用
收藏
页码:199 / 209
页数:11
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