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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.
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页码:131 / 140
页数:10
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