黑猩猩腺病毒和修饰的痘苗安卡拉病毒载体中编码的多种HBV

StephenW

Vaccines (Basel). 2020 Apr 14;8(2). pii: E184. doi: 10.3390/vaccines8020184.
The Design and Development of a Multi-HBV Antigen Encoded in Chimpanzee Adenoviral and Modified Vaccinia Ankara Viral Vectors; A Novel Therapeutic Vaccine Strategy against HBV.
Chinnakannan SK1, Cargill TN1, Donnison TA1, Ansari MA2, Sebastian S3, Lee LN1, Hutchings C1, Klenerman P1, Maini MK4, Evans T3, Barnes E1.
Author information

1
    Peter Medawar Building, Nuffield Department of Medicine, University of Oxford, Oxford OX1 3SY, UK.
2
    Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
3
    Vaccitech, The Oxford Science Park, The Schrodinger Building, Heatley Road, Oxford OX4 4GE, UK.
4
    Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, London WC1E 6JF, UK.

Abstract

Chronic hepatitis B virus (HBV) infection affects 257 million people globally. Current therapies suppress HBV but viral rebound occurs on cessation of therapy; novel therapeutic strategies are urgently required. To develop a therapeutic HBV vaccine that can induce high magnitude T cells to all major HBV antigens, we have developed a novel HBV vaccine using chimpanzee adenovirus (ChAd) and modified vaccinia Ankara (MVA) viral vectors encoding multiple HBV antigens. ChAd vaccine alone generated very high magnitude HBV specific T cell responses to all HBV major antigens. The inclusion of a shark Invariant (SIi) chain genetic adjuvant significantly enhanced the magnitude of T-cells against HBV antigens. Compared to ChAd alone vaccination, ChAd-prime followed by MVA-boost vaccination further enhanced the magnitude and breadth of the vaccine induced T cell response. Intra-cellular cytokine staining study showed that HBV specific CD8+ and CD4+ T cells were polyfunctional, producing combinations of IFNγ, TNF-α, and IL-2. In summary, we have generated genetically adjuvanted ChAd and MVA vectored HBV vaccines with the potential to induce high-magnitude T cell responses through a prime-boost therapeutic vaccination approach. These pre-clinical studies pave the way for new studies of HBV therapeutic vaccination in humans with chronic hepatitis B infection.
KEYWORDS:

ChAd; ChAdOx1; Hepatitis B virus (HBV); MVA; T cell vaccine; chimpanzee adenovirus; modified vaccinia Ankara; therapeutic HBV vaccine

PMID:
    32295168
DOI:
    10.3390/vaccines8020184

StephenW

疫苗（巴塞尔）。 2020年4月14日； 8（2）。号码：E184。土井：10.3390 /疫苗8020184。
黑猩猩腺病毒和修饰的痘苗安卡拉病毒载体中编码的多种HBV抗原的设计和开发；一种针对乙肝的新型治疗性疫苗策略。
Chinnakannan SK1，Cargill TN1，Donnison TA1，Ansari MA2，Sebastian S3，Lee LN1，Hutchings C1，Klenerman P1，Maini MK4，Evans T3，Barnes E1。
作者信息

1个
英国牛津大学牛津大学纳菲尔德分校彼得·梅达瓦尔（Peter Medawar）大楼，牛津OX1 3SY。
2
英国牛津大学牛津大学惠康人类遗传学中心OX3 7BN。
3
Vaccitech，牛津科学园，Schrodinger大楼，希特利路，牛津OX4 4GE，英国。
4
伦敦大学学院免疫与移植研究所感染与免疫科，英国伦敦WC1E 6JF。

抽象

慢性乙型肝炎病毒（HBV）感染在全球影响2.57亿人。目前的疗法可抑制HBV，但停止治疗后会出现病毒反弹。迫切需要新的治疗策略。为了开发一种可诱导所有主要HBV抗原诱导高强度T细胞的治疗性HBV疫苗，我们已经开发了一种新的HBV疫苗，它使用了黑猩猩腺病毒（ChAd）和修饰的牛痘安卡拉（MVA）病毒载体编码多种HBV抗原。单独的ChAd疫苗对所有HBV主要抗原产生了非常高的HBV特异性T细胞应答。鲨鱼不变（SIi）链遗传佐剂的加入显着增强了针对HBV抗原的T细胞的大小。与单独进行ChAd疫苗接种相比，ChAd-prime继之以MVA-boost疫苗接种进一步增强了疫苗诱导的T细胞反应的强度和广度。细胞内细胞因子染色研究表明，HBV特异性CD8 +和CD4 + T细胞具有多功能性，可产生IFNγ，TNF-α和IL-2的组合。总之，我们已经产生了遗传佐剂的ChAd和MVA载体HBV疫苗，它们有可能通过初免-加强治疗疫苗接种方法诱导高强度T细胞反应。这些临床前研究为慢性乙型肝炎感染者进行HBV治疗性疫苗的新研究铺平了道路。
关键字：

ChAd; ChAdOx1;乙型肝炎病毒（HBV）； MVA； T细胞疫苗；黑猩猩腺病毒；改良牛痘安卡拉;治疗性乙肝病毒疫苗

PMID：
32295168
DOI：
10.3390 /疫苗8020184

StephenW

https://www.mdpi.com/2076-393X/8/2/184/pdf