病毒学
抗体
表位
免疫原性
抗体效价
免疫系统
佐剂
中和抗体
重组DNA
免疫
效价
生物
体液免疫
免疫
病毒
免疫学
微生物学
生物化学
基因
作者
Feng Tian,Mingzhi Li,Lirong Zhang,Sha Li,Zibing Yang,Lumei Kang,Yunli Guo,Lingbao Kong,Ting Wang
出处
期刊:Vaccine
[Elsevier]
日期:2022-10-01
卷期号:40 (43): 6277-6287
被引量:1
标识
DOI:10.1016/j.vaccine.2022.09.020
摘要
Hepatitis C virus (HCV) infection remains a serious public health burden around the world. So far there is no effective vaccine against this virus. Neutralizing antibody (NAb) responses to the epitopes within HCV E1 and E2 proteins are related to the resolution of hepatitis C infection. E. coli heat-labile enterotoxin B subunit (LTB) has been described as potent immunity adjuvants. In this study, we constructed recombinant pET vectors: pET-R9-Bp (B cell polyepitopes) expressing 7 epitopes from HCV E1 and E2 proteins including R9 (E2384-411aa)-Bp (E1313-327aa-E2396-424aa-E2436-447aa-E2523-540aa-E2610-627aa-E2631-648aa) and pET-LTB-R9-Bp expressing LTB adjuvant in combination with R9-Bp. Recombinant proteins R9-Bp and LTB-R9-Bp were expressed successfully in E. coli and purified by the Ni-NTA column. Both R9-Bp and LTB-R9-Bp in BALB/c mice induced robust humoral immune response in the context of intraperitoneal or intramuscular immunization but not oral immunization. Intraperitoneal administration of LTB-R9-Bp induced a higher antibody titer (peak titer: 1:341000) than that of R9-Bp (peak titer: 1:85000) after the second boost (P = 0.0036 or 0.0002). However, comparable antibody peak titers were elicited for both R9-Bp and LTB-R9-Bp in intramuscular immunization albeit with significant difference (P = 0.0032) a week after the second boost. In addition, both R9-Bp and LTB-R9-Bp induced the secretion of cytokines including IFN-γ and IL-4 at similar levels. anti-sera induced by both R9-Bp and LTB-R9-Bp recognized native HCV E1 and E2 proteins. Moreover, these HCV-specific antisera inhibited significantly the entry of HCV (P < 0.0001). Taken together, these findings showed that E. coli-based both R9-Bp and LTB-R9-Bp could become promising HCV vaccines.
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