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Dna immunization with fusion of ctla-4 to hepatitis b virus (hbv) core protein enhanced th2 type responses and cleared hbv with an accelerated kinetic
Yin, Ying1; Wu, Chunchen2; Song, Jingjiao3; Wang, Junzhong3; Zhang, Ejuan1; Liu, Hongyan4; Yang, Dongliang3; Chen, Xinwen2; Lu, Mengji1,4; Xu, Yang1
刊名Plos one
2011-07-22
卷号6期号:7页码:11
ISSN号1932-6203
DOI10.1371/journal.pone.0022524
通讯作者Yin, ying()
英文摘要Background: typically, dna immunization via the intramuscular route induces specific, th1-dominant immune responses. however, plasmids expressing viral proteins fused to cytotoxic t lymphocyte antigen 4 (ctla-4) primed th2-biased responses and were able to induced effective protection against viral challenge in the woodchuck model. thus, we addressed the question in the mouse model how the th1/th2 bias of primed immune responses by a dna vaccine influences hepatitis b virus (hbv) clearance. principal findings: plasmids expressing hbv core protein (hbcag) or hbv e antigen and hbcag fused to the extracellular domain of ctla-4 (pctla-4-hbc), cd27, and full length cd40l were constructed. immunizations of these dna plasmids induced hbcag-specific antibody and cytotoxic t-cell responses in mice, but with different characteristics regarding the titers and subtypes of specific antibodies and intensity of t-cell responses. the plasmid phbc expressing hbcag induced an igg2a-dominant response while immunizations of pctla-4-hbc induced a balanced igg1/igg2a response. to assess the protective values of the immune responses of different characteristics, mice were pre-immunized with pctla-4-hbc and phbc, and challenged by hydrodynamic injection (hi) of paav/hbv1.2. hbv surface antigen (hbsag) and dna in peripheral blood and hbcag in liver tissue were cleared with significantly accelerated kinetics in both groups. the clearance of hbsag was completed within 16 days in immunized mice while more than 50% of the control mice are still positive for hbsag on day 22. stronger hbcag-specific t-cell responses were primed by phbc correlating with a more rapid decline of hbcag expression in liver tissue, while anti-hbs antibody response developed rapidly in the mice immunized with pctla-4-hbc, indicating that the th1/th2 bias of vaccine-primed immune responses influences the mode of viral clearance. conclusion: viral clearance could be efficiently achieved by th1/th2-balanced immune response, with a small but significant shift in t-cell and b-cell immune responses.
WOS关键词HIV GAG PROTEIN ; CD8(+) T-CELLS ; ANTITUMOR IMMUNITY ; DENDRITIC CELLS ; IMMUNODEFICIENCY-VIRUS ; TARGETED DELIVERY ; DEC-205 RECEPTOR ; GAMMA-INTERFERON ; SURFACE-ANTIGEN ; TUMOR-ANTIGENS
WOS研究方向Science & Technology - Other Topics
WOS类目Multidisciplinary Sciences
语种英语
出版者PUBLIC LIBRARY SCIENCE
WOS记录号WOS:000293097300060
内容类型期刊论文
URI标识http://www.corc.org.cn/handle/1471x/2375941
专题武汉病毒研究所
通讯作者Yin, Ying
作者单位1.Huazhong Univ Sci & Technol, Dept Microbiol, Tongji Med Coll, Wuhan 430074, Peoples R China
2.Chinese Acad Sci, Wuhan Inst Virol, Wuhan, Peoples R China
3.Huazhong Univ Sci & Technol, Div Clin Immunol, Tongji Hosp, Wuhan 430074, Peoples R China
4.Univ Hosp Essen, Inst Virol, Essen, Germany
推荐引用方式
GB/T 7714
Yin, Ying,Wu, Chunchen,Song, Jingjiao,et al. Dna immunization with fusion of ctla-4 to hepatitis b virus (hbv) core protein enhanced th2 type responses and cleared hbv with an accelerated kinetic[J]. Plos one,2011,6(7):11.
APA Yin, Ying.,Wu, Chunchen.,Song, Jingjiao.,Wang, Junzhong.,Zhang, Ejuan.,...&Xu, Yang.(2011).Dna immunization with fusion of ctla-4 to hepatitis b virus (hbv) core protein enhanced th2 type responses and cleared hbv with an accelerated kinetic.Plos one,6(7),11.
MLA Yin, Ying,et al."Dna immunization with fusion of ctla-4 to hepatitis b virus (hbv) core protein enhanced th2 type responses and cleared hbv with an accelerated kinetic".Plos one 6.7(2011):11.
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