免疫原性对HBsAg和HLA-人源化转基因小鼠模型中主要HBV抗原的

StephenW

Euroasian J Hepatogastroenterol. 2014 Jan-Jun;4(1):36-44. doi: 10.5005/jp-journals-10018-1094. Epub  2014 Jan 22.
Impact of the Immunogen Nature on the Immune Response against the Major HBV Antigens in an HBsAg and HLA-humanized Transgenic Mouse Model.Mancini-Bourgine M1, Guillen G2, Michel ML1, Aguilar JC2.
Author information
1Laboratoire de Pathogenese des virus de l'hepatite B, Institut Pasteur, Paris, France; Inserm U845, Unite de Pathogenese des hepatites virales B et Immunotherapie, Paris, France.2Vaccine Division, Clinical Trials Department, Center for Genetic Engineering and Biotechnology, Havana City, Cuba.

AbstractHepatitis B chronic carriage remains as a major public health problem. Protein and DNA vaccines are now widely used in therapeutic vaccine candidates. Although, the hepatitis B surface antigen (HBsAg) based vaccines have been largely studied, candidates comprising both HBsAg and core (HBcAg) either protein- or DNA-based approaches deserve further immunological characterization. In the present study, a repeated dose administration schedule for protein or DNA immunogens was conducted in order to characterize the resulting immune response in a humanized and HBsAg-tolerized setting. A novel transgenic (Tg) mice that express the HBsAg, human MHC class I (HLA-A*0201) and MHC class II (HLA-DRB1*01) molecules and devoid of endogenous murine class I and II molecules was used as a model of HBV chronic carrier. Mice were immunized by subcutaneous (protein) or intramuscular (DNA) routes and the humoral and cellular responses were evaluated. Protein or DNA immunization induced humoral immune responses against both HBsAg and HBcAg. The systematic analysis of epitopes that activate CD4+ and CD8+ T lymphocytes confirmed the accuracy of the model. Cellular immune responses were detected differing in their nature. CD8 T-cell responses were induced mostly after DNA immunization while CD4 T-cell responses were predominant in protein based immunizations. In addition, the intensity of HLA-A2-restricted CD8+ T cell responses was reduced in Tg mice expressing HBsAg when compared to control Tg mice. In conclusion, our results indicate that cellular immune responses necessary for the development of protective immunity can be achieved by DNA or protein immunization. However, important differences in their nature arise when immunogens are administered several times. How to cite this article: Mancini-Bourgine M, Guillen G, Michel ML, Aguilar JC. Impact of the Immunogen Nature on the Immune Response against the Major HBV Antigens in an HBsAg and HLA-humanized Transgenic Mouse Model. Euroasian J Hepato-Gastroenterol 2014;4(1):36-44.


KEYWORDS: Cellular immunity.; HBV; HBcAg; HBsAg; Humoral immunity; Immunogen; Transgenic mice

PMID:29264317PMCID:PMC5736954DOI:10.5005/jp-journals-10018-1094

StephenW

欧亚大陆J肝胃肠炎。 2014年1月 - 6月; 4（1）：36-44。 doi：10.5005 / jp-journals-10018-1094。电子书2014年1月22日。
免疫原性对HBsAg和HLA-人源化转基因小鼠模型中主要HBV抗原的免疫应答的影响。
Mancini-Bourgine M1，Guillen G2，Michel ML1，Aguilar JC2。
作者信息

1
    法国巴黎巴斯德研究所病毒病研究所病毒实验室; Inserm U845，Unite de Pathogenese des hepatites virales B et Immunotherapie，Paris，France。
2
    古巴哈瓦那市基因工程和生物技术中心临床试验部门疫苗部门。

抽象

乙型肝炎慢性运输仍然是一个重大的公共卫生问题。现在蛋白质和DNA疫苗广泛用于治疗候选疫苗。尽管基于乙肝表面抗原（HBsAg）的疫苗已经被大量研究，但包含HBsAg和核心（HBcAg）蛋白或基于DNA的方法的候选者都需要进一步的免疫学表征。在本研究中，进行蛋白质或DNA免疫原的重复给药方案，以表征在人源化和HBsAg耐受环境中产生的免疫应答。将表达HBsAg，人类MHC I类（HLA-A * 0201）和MHC II类（HLA-DRB1 * 01）分子且缺乏内源性鼠类I和II分子的新型转基因（Tg）小鼠用作模型HBV慢性携带者。通过皮下（蛋白质）或肌内（DNA）途径免疫小鼠，评估体液和细胞反应。蛋白或DNA免疫诱导针对HBsAg和HBcAg的体液免疫应答。激活CD4 +和CD8 + T淋巴细胞表位的系统分析证实了模型的准确性。检测到细胞免疫应答的性质不同。 CD8 T细胞应答主要在DNA免疫后被诱导，而CD4 T细胞应答在基于蛋白质的免疫中是主要的。另外，与对照Tg小鼠相比，表达HBsAg的Tg小鼠中HLA-A2限制性CD8 + T细胞应答的强度降低。总之，我们的结果表明，通过DNA或蛋白质免疫可以实现保护性免疫发展所必需的细胞免疫应答。然而，当免疫原多次施用时，其性质的重要差异就会出现。如何引用这篇文章：曼奇尼 - Bourgine M，吉伦G，米歇尔ML，阿吉拉尔JC。免疫原性对HBsAg和HLA-人源化转基因小鼠模型中主要HBV抗原的免疫应答的影响。 Euroasian J Hepato-Gastroenterol 2014; 4（1）：36-44。
关键词：

细胞免疫。 HBV;核心抗原;乙肝表面抗原;体液免疫;免疫原;转基因小鼠

结论：
    29264317
PMCID：
    PMC5736954
DOI：
    10.5005 / JP-期刊-10018-1094