Chimeric virus-like particles containing a conserved region of the G protein in combination with a single peptide of the M2 protein confer protection against respiratory syncytial virus infection

被引:14
作者
Qiao, Lei [1 ]
Zhang, Yuan [1 ]
Chai, Feng [1 ]
Tan, Yiluo [1 ]
Huo, Chunling [1 ]
Pan, Zishu [1 ]
机构
[1] Wuhan Univ, Coll Life Sci, State Key Lab Virol, Wuhan 430072, Peoples R China
基金
国家高技术研究发展计划(863计划);
关键词
Respiratory syncytial virus (RSV); Virus like particle (VLP); Lung pathology; RSV attachment glyco (G) protein; Hepatitis B virus core protein (HBc); Subunit vaccine; T-CELL RESPONSES; ATTACHMENT G GLYCOPROTEIN; VACCINE-ENHANCED DISEASE; IMMUNIZED BALB/C MICE; PULMONARY EOSINOPHILIA; RSV CHALLENGE; ANTIBODY-RESPONSES; COTTON RATS; TNF-ALPHA; F-PROTEIN;
D O I
10.1016/j.antiviral.2016.05.001
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
To investigate the feasibility and efficacy of a virus-like particle (VLP) vaccine composed of the conserved antigenic epitopes of respiratory syncytial virus (RSV), the chimeric RSV VLPs HBc Delta-tG and HBc Delta-tG/M2(82-90) were generated based on the truncated hepatitis B virus core protein (HBc Delta). HBc Delta-tG consisted of HBc Delta, the conserved region (aa 144-204) of the RSV G protein. HBc Delta-tG was combined with a single peptide (aa 82-90) of the M2 protein to generate HBc Delta-tG/M2(82-90). Immunization of mice with the HBc Delta-tG or HBc Delta-tG/M2(82-90) VLPs elicited RSV-specific IgG and neutralizing antibody production and conferred protection against RSV infection. Compared with HBc Delta-tG, HBc Delta-tG/M2(82-90) induced decreased Th2 cytokine production (IL-4 and IL-5), increased Th1 cytokine response (IFN-gamma, TNF-alpha, and IL-2), and increased ratios of IgG2a/IgG1 antibodies, thereby relieving pulmonary pathology upon subsequent RSV infection. Our results demonstrated that chimeric HBc Delta 4G/M2(82-90) VLPs represented an effective RSV subunit vaccine candidate. (C) 2016 Elsevier B.V. All rights reserved.
引用
收藏
页码:131 / 140
页数:10
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