改良的α病毒-疱疹病毒混合疫苗载体用于慢性乙型肝炎的同

StephenW

  Modified Alphavirus-Vesiculovirus Hybrid Vaccine Vectors for Homologous Prime-Boost Immunotherapy of Chronic Hepatitis B
Carolina Chiale  1 , Timur O Yarovinsky  2   3 , Stephen W Mason  3 , Bhaskara R Madina  3 , Manisha Menon  3 , Marie M Krady  3 , Safiehkhatoon Moshkani  1 , Anasuya Chattopadhyay Pal  2 , Bijan Almassian  3 , John K Rose  2 , Michael D Robek  1 , Valerian Nakaar  3
Affiliations
Affiliations

    1
    Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
    2
    Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.
    3
    CaroGen Corporation, Farmington, CT 06032, USA.

    PMID: 32517032 DOI: 10.3390/vaccines8020279
Abstract： Virus-like vesicles (VLV) are hybrid vectors based on an evolved Semliki Forest virus (SFV) RNA replicon and the envelope glycoprotein (G) from vesicular stomatitis virus (VSV). Previously, we showed that VLV can be used to express protein antigens and generate protective antigen-specific CD8+ T cells. This report describes VLV vectors designed for enhanced protein expression and immunogenicity. Expressing hepatitis B virus (HBV) middle S antigen (MHBs) from VLV using a dual subgenomic promoter significantly increased MHBs-specific CD8+ T cell and antibody production in mice. Furthermore, envelope glycoprotein switch from VSV Indiana to the glycoprotein of Chandipura virus enabled prime-boost immunization and further increased responses to MHBs. Therapeutic efficacy was evaluated in a mouse model of chronic HBV infection initiated by HBV delivery with adeno-associated virus. Mice with lower or intermediate HBV antigen levels demonstrated a significant and sustained reduction of HBV replication following VLV prime-boost immunization. However, mice with higher HBV antigen levels showed no changes in HBV replication, emphasizing the importance of HBV antigenemia for implementing immunotherapies. This report highlights the potential of VLV dual promoter vectors to induce effective antigen-specific immune responses and informs the further development and evaluation of hybrid viral vaccine platforms for preventative and therapeutic purposes.
Keywords: hepatitis B virus; vesicular stomatitis virus; RNA replicon; immunotherapy

StephenW

改良的α病毒-疱疹病毒混合疫苗载体用于慢性乙型肝炎的同源初免-加强免疫治疗
卡罗来纳州Chiale 1，Timur O Yarovinsky 2 3，Stephen W Mason 3，Bhaskara R Madina 3，Manisha Menon 3，Marie M Krady 3，Safiehkhatoon Moshkani 1，Anasuya Chattopadhyay Pal 2，Bijan Almassian 3，John K Rose 2，Michael D Robek 1，缬草纳卡尔3
隶属关系
隶属关系

    1个
    美国纽约州奥尔巴尼市奥尔巴尼医学院免疫学和微生物病系。
    2
    耶鲁大学医学院病理学系，美国康涅狄格州纽黑文06510。
    3
    CaroGen Corporation，法明顿，CT 06032，美国。

    PMID：32517032 DOI：10.3390 / vaccines8020279
摘要：病毒样小泡（VLV）是基于进化的Semliki森林病毒（SFV）RNA复制子和水泡性口炎病毒（VSV）的包膜糖蛋白（G）的杂交载体。以前，我们表明VLV可用于表达蛋白质抗原并产生保护性抗原特异性CD8 + T细胞。该报告描述了设计用于增强蛋白表达和免疫原性的VLV载体。使用双亚基因组启动子从VLV表达乙型肝炎病毒（HBV）中S抗原（MHBs），可显着增加小鼠中MHBs特异性CD8 + T细胞和抗体的产生。此外，包膜糖蛋白从VSV印第安纳州转换为钱迪普拉病毒的糖蛋白，可以进行初免-加强免疫，并进一步增强了对MHBs的反应。在慢性HBV感染的小鼠模型中评估了治疗效果，该模型是由腺相关病毒通过HBV递送引发的。 VLV初免-加强免疫后，具有较低或中等HBV抗原水平的小鼠表现出明显且持续的HBV复制减少。但是，具有较高HBV抗原水平的小鼠未显示HBV复制的变化，强调了HBV抗原血症对实施免疫疗法的重要性。该报告强调了VLV双启动子载体诱导有效抗原特异性免疫反应的潜力，并为预防和治疗目的进一步开发和评估了混合病毒疫苗平台。
关键词：乙型肝炎病毒；水泡性口炎病毒； RNA复制子；免疫疗法