Prompt and Robust Humoral Immunity Elicited by a Conjugated Chimeric Malaria Antigen with a Truncated Flagellin
文献类型：期刊论文
| 作者 | Guo, Fangxia1,2; Liu, Yongdong1; Zhang, Chun1; Wang, Qi1,2; Wang, Lianyan1; Gao, Yuhui3; Bi, Jingxiu4; Wang, Heng3; Su, Zhiguo1 |
| 刊名 | BIOCONJUGATE CHEMISTRY
 |
| 出版日期 | 2018-03-01 |
| 卷号 | 29期号:3页码:761-770 |
| ISSN号 | 1043-1802 |
| DOI | 10.1021/acs.bioconjchem.7b00320 |
| 文献子类 | Article |
| 英文摘要 | As one of the pathogen-associated molecular patterns (PAMPs), flagellin is recently utilized as a potent adjuvant for many subunit vaccines. In this study, a truncated flagellin (tFL) with deletion of the hypervariable regions was adopted as a carrier-adjuvant by chemical conjugation with a chimeric malaria antigen M.RCAg-1 (M312) via a heterobifunctional polyethylene glycol (PEG) linker. After booster immunization in mice without any extra adjuvants, the M312-PEG-tFL conjugates elicited M312-specific antibody titers 100-1000 times higher than M312 and 10-100 times higher than the physical mixture of M312 and tFL. The elicited specific antibodies could recognize the native parasites, and the immunofluorescence assay (IFA) titer was 2100 for M312-P5k-tFL, which was about 7 times higher than M312. Furthermore, the IFA titers of the conjugates were comparable to the positive control of complete Freund's adjuvant (CFA). Compared to M312, the M312-PEG-tFL conjugates enhanced the proliferation index, lymphocyte activation, and memory T-cell generation. IgG subclasses of sera and cytokines analysis of splenocytes showed that conjugation with tFL could slightly trigger the Th1 polarization, while the antigen alone predominantly induced a Th2-biased immune response. Furthermore, a more-efficient innate immune response was provoked by the M312-PEG-tFL conjugates, as determined by the detection of antigen-specific TNF-alpha secretion by splenocytes. Our results indicated that tFL mainly retained the function as an agonist of TLR5. Conjugation of antigen to tFL could induce strong humoral and moderate cellular immune responses. Thus, conjugation of antigen to tFL as a potent carrier-adjuvant is an effective strategy for developing a promising protein-based vaccine. |
| WOS关键词 | TOLL-LIKE RECEPTOR-5 ; VACCINE CANDIDATE ; ANTIBODY-RESPONSE ; INNATE IMMUNITY ; FUSION PROTEIN ; ADJUVANT ; IMMUNOGENICITY ; TRANSMISSION ; ACTIVATION ; AGONIST |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000428356300019 |
| 资助机构 | National Science and Technology Major Project of "National Key Program on Drug Innovation"(2013ZX09102-043) ; National Natural Science Foundation of China(21576267) ; Beijing National Science Foundation(2162041) ; Major State Basic Research Development Program of China(2013CB733604) |
| 源URL | [http://ir.ipe.ac.cn/handle/122111/24147]  |
| 专题 | 过程工程研究所_生化工程国家重点实验室 |
| 作者单位 | 1.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Chinese Acad Med Sci, Inst Basic Med Sci, Peking Union Med Coll, Mol Parasitol Lab, Beijing 100005, Peoples R China 4.Univ Adelaide, Sch Chem Engn, Adelaide, SA 5005, Australia |
| 推荐引用方式 GB/T 7714 | Guo, Fangxia,Liu, Yongdong,Zhang, Chun,et al. Prompt and Robust Humoral Immunity Elicited by a Conjugated Chimeric Malaria Antigen with a Truncated Flagellin[J]. BIOCONJUGATE CHEMISTRY,2018,29(3):761-770. |
| APA | Guo, Fangxia.,Liu, Yongdong.,Zhang, Chun.,Wang, Qi.,Wang, Lianyan.,...&Su, Zhiguo.(2018).Prompt and Robust Humoral Immunity Elicited by a Conjugated Chimeric Malaria Antigen with a Truncated Flagellin.BIOCONJUGATE CHEMISTRY,29(3),761-770. |
| MLA | Guo, Fangxia,et al."Prompt and Robust Humoral Immunity Elicited by a Conjugated Chimeric Malaria Antigen with a Truncated Flagellin".BIOCONJUGATE CHEMISTRY 29.3(2018):761-770. |
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来源：过程工程研究所
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