Bonafé Nathalie, Rininger Joseph A, Chubet Richard G, Foellmer Harald G, Fader Stacey, Anderson John F, Bushmich Sandra L, Anthony Karen, Ledizet Michel, Fikrig Erol, Koski Raymond A, Kaplan Paul
L2 Diagnostics, LLC, 300 George Street, New Haven, CT 06511, USA.
Vaccine. 2009 Jan 7;27(2):213-22. doi: 10.1016/j.vaccine.2008.10.046. Epub 2008 Nov 7.
In this study, a recombinant truncated West Nile virus envelope protein antigen (rWNV-E) was produced in serum-free cultures of the expresSF+ insect cell line via baculovirus infection. This production system was selected based on its use in the production of candidate human and animal vaccine antigens. A defined fermentation and purification process for the rWNV-E antigen was established to control for purity and immunogenicity of each protein batch. The material formulated with aluminum hydroxide was stable for greater than 8months at 4 degrees C. The recombinant vaccine candidate was evaluated for immunogenicity and protective efficacy in several animal models. In mouse and hamster WNV challenge models, the vaccine candidate induced viral protection that correlated with anti-rWNV-E immunogenicity and WNV neutralizing antibody titers. The rWNV-E vaccine candidate was used to boost horses previously immunized with the Fort Dodge inactivated WNV vaccine and also to induce WNV neutralizing titers in naïve foals that were at least 14weeks of age. Furthermore, the vaccine candidate was found safe when high doses were injected into rats, with no detectable treatment-related clinical adverse effects. These observations demonstrate that baculovirus-produced rWNV-E can be formulated with aluminum hydroxide to produce a stable and safe vaccine which induces humoral immunity that can protect against WNV infection.
在本研究中,通过杆状病毒感染,在无血清培养的expresSF+昆虫细胞系中生产了重组截短型西尼罗河病毒包膜蛋白抗原(rWNV-E)。选择该生产系统是基于其在生产候选人和动物疫苗抗原方面的应用。建立了rWNV-E抗原的确定发酵和纯化工艺,以控制每批蛋白质的纯度和免疫原性。用氢氧化铝配制的材料在4℃下稳定超过8个月。在几种动物模型中评估了重组候选疫苗的免疫原性和保护效力。在小鼠和仓鼠西尼罗河病毒攻击模型中,候选疫苗诱导了与抗rWNV-E免疫原性和西尼罗河病毒中和抗体滴度相关的病毒保护作用。rWNV-E候选疫苗用于增强先前用福道奇灭活西尼罗河病毒疫苗免疫的马匹的免疫力,也用于诱导至少14周龄的未免疫幼驹产生西尼罗河病毒中和滴度。此外,当向大鼠注射高剂量时,发现候选疫苗是安全的,没有可检测到的与治疗相关的临床不良反应。这些观察结果表明,杆状病毒产生的rWNV-E可以与氢氧化铝配制,以生产一种稳定且安全的疫苗,该疫苗可诱导体液免疫,从而预防西尼罗河病毒感染。