未经批准:诱导强效,HBV特异性免疫应答对于控制和最终治愈HBV至关重要。治疗性乙型肝炎疫苗TherVacB结合蛋白质引发与改良的痘苗病毒安卡拉(MVA)载体增强,以打破慢性HBV感染的免疫耐受。颗粒蛋白和载体疫苗成分,然而,需要一个恒定的冷却链进行存储和运输,对疫苗应用构成后勤和财务挑战。我们旨在使用系统方法鉴定维持疫苗的蛋白质和载体组分的稳定性和免疫原性的最佳制剂。
UASSIGNED:我们使用稳定氨基酸(SAA)为基础的配方来稳定HBsAg和HBV核心颗粒(HBcAg),和MVA载体。然后我们研究了冻干和短期和长期高温储存对其完整性的影响。在HBV感染和腺相关病毒(AAV)-HBV感染的小鼠中验证了配制疫苗的免疫原性和安全性。
UNASSIGNED:体外分析证明了疫苗在冻干过程中对热应力的稳定性和SAA配制的HBsAg的长期稳定性,在40°C下3个月和25°C下12个月的热应力期间的HBcAg和MVA。未接种HBV和AAV-HBV感染的小鼠的疫苗接种表明,稳定的疫苗具有良好的耐受性,并且能够像在4°C/-80°C下持续储存的疫苗成分一样有效地阻止在AAV-HBV小鼠中建立的免疫耐受。即使长期暴露在高温下,稳定的TherVacB诱导高滴度HBV特异性抗体和强CD8+T细胞反应,导致抗HBs血清转换和HBV复制小鼠中病毒的强烈抑制。
未经证实:SAA配方导致高度功能性和热稳定的HBsAg,HBcAg和MVA疫苗组分。这将促进全球疫苗的应用,而无需冷却链,并且对于开发支持全球疫苗接种运动的预防性和治疗性疫苗非常重要。
UNASSIGNED:治疗性疫苗接种是慢性乙型肝炎的一种有希望的治疗选择,可能使其治愈。然而,它的应用需要在运输和存储过程中的功能性冷却链,这在许多需求高的国家很难保证。在这项研究中,作者开发了热稳定的疫苗成分,这些成分具有良好的耐受性,可以在临床前小鼠模型中诱导免疫反应并控制病毒,即使长期暴露在高温环境中。这将降低成本并简化治疗性疫苗的应用,从而对全世界许多受乙型肝炎影响的人有益。
UNASSIGNED: Induction of potent, HBV-specific immune responses is crucial to control and finally cure HBV. The therapeutic hepatitis B vaccine TherVacB combines protein priming with a Modified Vaccinia virus Ankara (MVA)-vector boost to break immune tolerance in chronic HBV infection. Particulate protein and vector vaccine components, however, require a constant cooling chain for storage and transport, posing logistic and financial challenges to vaccine applications. We aimed to identify an optimal formulation to maintain stability and immunogenicity of the protein and vector components of the vaccine using a systematic approach.
UNASSIGNED: We used stabilizing amino acid (SAA)-based formulations to stabilize HBsAg and HBV core particles (HBcAg), and the MVA-vector. We then investigated the effect of lyophilization and short- and long-term high-temperature storage on their integrity. Immunogenicity and safety of the formulated vaccine was validated in HBV-naïve and adeno-associated virus (AAV)-HBV-infected mice.
UNASSIGNED: In vitro analysis proved the vaccine\'s stability against thermal stress during lyophilization and the long-term stability of SAA-formulated HBsAg, HBcAg and MVA during thermal stress at 40 °C for 3 months and at 25 °C for 12 months. Vaccination of HBV-naïve and AAV-HBV-infected mice demonstrated that the stabilized vaccine was well tolerated and able to brake immune tolerance established in AAV-HBV mice as efficiently as vaccine components constantly stored at 4 °C/-80 °C. Even after long-term exposure to elevated temperatures, stabilized TherVacB induced high titre HBV-specific antibodies and strong CD8+ T-cell responses, resulting in anti-HBs seroconversion and strong suppression of the virus in HBV-replicating mice.
UNASSIGNED: SAA-formulation resulted in highly functional and thermostable HBsAg, HBcAg and MVA vaccine components. This will facilitate global vaccine application without the need for cooling chains and is important for the development of prophylactic as well as therapeutic vaccines supporting vaccination campaigns worldwide.
UNASSIGNED: Therapeutic vaccination is a promising therapeutic option for chronic hepatitis B that may enable its cure. However, its application requires functional cooling chains during transport and storage that can hardly be guaranteed in many countries with high demand. In this study, the authors developed thermostable vaccine components that are well tolerated and that induce immune responses and control the virus in preclinical mouse models, even after long-term exposure to high surrounding temperatures. This will lower costs and ease application of a therapeutic vaccine and thus be beneficial for the many people affected by hepatitis B around the world.