Department of Pathology, Yale University School of Medicine, New Haven, Conneticut 06520-8023, USA.
J Virol. 2010 Aug;84(15):7513-22. doi: 10.1128/JVI.00200-10. Epub 2010 May 26.
As one of the world's most common infectious diseases, hepatitis B virus (HBV) is a serious worldwide public health problem, with HBV-associated liver disease accounting for more than half a million deaths each year. Although there is an effective prophylactic vaccine currently available to prevent infection, it has a number of characteristics that are suboptimal: multiple doses are needed to induce long-lasting immunity, immunity declines over time, it does not elicit protection in some individuals, and it is not effective therapeutically. We produced a recombinant vesicular stomatitis virus (VSV)-based vaccine vector expressing the HBV middle envelope surface protein (MS) and found that this vector was able to efficiently generate a strong HBs-specific antibody response following a single immunization in mice. A single immunization with the VSV-MS vector also induced robust CD8 T-cell activation. The CD8 T-cell response was greater in magnitude and broader in specificity than the response generated by a vaccinia virus-based vaccine vector or by recombinant protein immunization. Furthermore, a single VSV-MS immunization provided protection against virus challenge in mice. Given the similar antibody titers and superior T-cell responses elicited from a single immunization, a VSV-based HBV vaccine may have advantages over the current recombinant protein vaccine.
作为世界上最常见的传染病之一,乙型肝炎病毒(HBV)是一个严重的全球公共卫生问题,每年有超过 50 万人因 HBV 相关肝病而死亡。虽然目前有有效的预防性疫苗可用于预防感染,但它有一些不理想的特点:需要多次接种才能诱导持久的免疫力,免疫力随时间下降,在一些人中不能引发保护作用,并且在治疗上无效。我们生产了一种表达 HBV 中包膜表面蛋白(MS)的重组水疱性口炎病毒(VSV)疫苗载体,发现该载体在单次免疫小鼠后能够有效地产生强烈的 HBs 特异性抗体反应。单次免疫 VSV-MS 载体也诱导了强烈的 CD8 T 细胞激活。CD8 T 细胞反应的强度和特异性都比痘苗病毒载体或重组蛋白免疫产生的反应更大。此外,单次 VSV-MS 免疫可提供针对病毒攻击的保护作用。鉴于单次免疫可产生相似的抗体滴度和更优的 T 细胞反应,VSV 为基础的 HBV 疫苗可能比目前的重组蛋白疫苗具有优势。