期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 534, 期 -, 页码 891-895出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2020.10.081
关键词
Hepatitis B virus Core protein (HBc); Virus-like particles (VLPs); Intein-mediated trans-splicing
资金
- National Key R&D Program of China [2016YFA0502101]
- National Natural Science Foundation of China [81371826, 81572002]
In this study, intein-mediated transsplicing was utilized to decorate HBc VLPs with antigens, improving solubility of recombinant protein and enabling spontaneous assembly into VLPs. Antigens delivered by HBc VLPs induced significantly enhanced antigen-specific immune responses.
Hepatitis B virus core protein (HBc) spontaneously assembles as Virus-like particles (VLPs) in Escherichia coli (E. coli) which is extensively used as a nanocarrier to boost antigen immunogenicity. Genetic fusion of cargo protein with HBc occasionally forms inclusion bodies instead of properly assembled VLPs. To this end, we devised HBc VLPs as a modular nanocarrier for antigen delivery by intein-mediated transsplicing (TS). We introduced split intein(C) (int(C)) to the C-terminus of split HBc N-core to employ inteinmediated TS technology to HBc VLPs. Split HBc with the insertion of int(C) at N-core C-terminus (designated as HBc N-int(C)-C) existed in inclusion bodies. Interestingly, introduction of a soluble tag, gb1, to int(C) C-terminus remarkably improved the solubility of recombinant protein (named HBc N-int(C)-gb1-C). Moreover, newly designed recombinant spontaneously assembled as VLPs and endowed efficiently coupling two different model antigens onto HBc N-int(C)-gb1-C VLPs. Furthermore, model antigens delivered by HBc VLPs induced a dramatically enhanced antigen-specific immune responses. Antigen proteins mainly elicited Th2 IgG responses while antigens delivered by HBc VLPs steered Th1/Th2 balanced IgG responses. Taken together, intein-mediated TS was amenable to decorate HBc VLPs with antigens and showed good potential for antigen delivery. (c) 2020 Elsevier Inc. All rights reserved.
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