在莴苣中产生的嵌合乙型肝炎病毒S / preS1抗原的口服给药在

StephenW

Vaccine. 2018 Aug 3. pii: S0264-410X(18)31081-8. doi: 10.1016/j.vaccine.2018.07.072. [Epub ahead of print]
Oral administration of a chimeric Hepatitis B Virus S/preS1 antigen produced in lettuce triggers infection neutralizing antibodies in mice.
Dobrica MO1, Lazar C1, Paruch L2, van Eerde A2, Clarke JL2, Tucureanu C3, Caras I3, Ciulean S3, Onu A3, Tofan V3, Branzan A4, Urban S5, Stavaru C3, Branza-Nichita N6.
Author information

1
    Institute of Biochemistry of the Romanian Academy, Bucharest, Romania.
2
    NIBIO - Norwegian Institute for Bioeconomy Research, Ås, Norway.
3
    "Cantacuzino" National Research Institute, Bucharest, Romania.
4
    Institute of Biology of the Romanian Academy, Bucharest, Romania.
5
    University Hospital Heidelberg, Germany.
6
    Institute of Biochemistry of the Romanian Academy, Bucharest, Romania. Electronic address: [email protected].

Abstract

Hepatitis B Virus (HBV) infection can be prevented by vaccination. Vaccines containing the small (S) envelope protein are currently used in universal vaccination programs and achieve protective immune response in more than 90% of recipients. However, new vaccination strategies are necessary for successful immunization of the remaining non- or low-responders. We have previously characterized a novel HBV chimeric antigen, which combines neutralization epitopes of the S and the preS1 domain of the large (L) envelope protein (genotype D). The S/preS121-47 chimera produced in mammalian cells and Nicotiana benthamiana plants, induced a significantly stronger immune response in parenterally vaccinated mice than the S protein. Here we describe the transient expression of the S/preS121-47 antigen in an edible plant, Lactuca sativa, for potential development of an oral HBV vaccine. Our study shows that oral administration of adjuvant-free Lactuca sativa expressing the S/preS121-47 antigen, three times, at 1 μg/dose, was sufficient to trigger a humoral immune response in mice. Importantly, the elicited antibodies were able to neutralize HBV infection in an NTCP-expressing infection system (HepG2-NTCP cell line) more efficiently than those induced by mice fed on Lactuca sativa expressing the S protein. These results support the S/preS121-47 antigen as a promising candidate for future development as an edible HBV vaccine.
KEYWORDS:

Edible vaccine; Hepatitis B Virus; Neutralizing antibody; Plant expression

PMID:
    30082163
DOI:
    10.1016/j.vaccine.2018.07.072

StephenW

疫苗。 2018年8月3日.pii：S0264-410X（18）31081-8。 doi：10.1016 / j.vaccine.2018.07.072。 [提前打印]
在莴苣中产生的嵌合乙型肝炎病毒S / preS1抗原的口服给药在小鼠中引发感染中和抗体。
Dobrica MO1，Lazar C1，Paruch L2，van Eerde A2，Clarke JL2，Tucureanu C3，Caras I3，Ciulean S3，Onu A3，Tofan V3，Branzan A4，Urban S5，Stavaru C3，Branza-Nichita N6。
作者信息

1
    罗马尼亚学院生物化学研究所，罗马尼亚布加勒斯特。
2
    NIBIO - 挪威Ås挪威生物经济研究所。
3
    “Cantacuzino”国家研究所，布加勒斯特，罗马尼亚。
4
    罗马尼亚学院生物学研究所，罗马尼亚布加勒斯特。
五
    德国海德堡大学医院。
6
    罗马尼亚学院生物化学研究所，罗马尼亚布加勒斯特。电子地址：[email protected]。

抽象

接种疫苗可以预防乙型肝炎病毒（HBV）感染。含有小（S）包膜蛋白的疫苗目前用于通用疫苗接种计划，并在超过90％的接受者中实现保护性免疫应答。然而，新的疫苗接种策略对于成功免疫剩余的非应答者或低应答者是必要的。我们先前已经表征了一种新的HBV嵌合抗原，其结合了S的中和表位和大（L）包膜蛋白（基因型D）的preS1结构域。在哺乳动物细胞和本塞姆氏烟草植物中产生的S / preS121-47嵌合体在肠胃外接种的小鼠中诱导比S蛋白显着更强的免疫应答。在这里，我们描述了可食用植物Lactuca sativa中S / preS121-47抗原的瞬时表达，用于口服HBV疫苗的潜在开发。我们的研究表明，在1μg/剂量下口服施用表达S / preS121-47抗原的无佐剂莴苣三次足以引发小鼠的体液免疫应答。重要的是，引发的抗体能够比表达S蛋白的莴苣（Lactuca sativa）饲喂的小鼠更有效地中和表达NTCP的感染系统（HepG2-NTCP细胞系）中的HBV感染。这些结果支持S / preS121-47抗原作为可食用HBV疫苗的未来发展的有希望的候选者。
关键词：

食用疫苗;乙型肝炎病毒;中和抗体;植物表达

结论：
    30082163
DOI：
    10.1016 / j.vaccine.2018.07.072