Legisa D M, Perez Aguirreburualde M S, Gonzalez F N, Marin-Lopez A, Ruiz V, Wigdorovitz A, Martinez-Escribano J A, Ortego J, Dus Santos M J
Instituto de Virología, CNIA Hurlingham (1686), Buenos Aires, Argentina.
Instituto de Virología, CNIA Hurlingham (1686), Buenos Aires, Argentina.
Vaccine. 2015 May 21;33(22):2614-9. doi: 10.1016/j.vaccine.2015.03.067. Epub 2015 Apr 6.
Bluetongue virus (BTV), the causative agent of bluetongue disease (BT) in domestic and wild ruminants, is worldwide distributed. A total of 27 serotypes have been described so far, and several outbreaks have been reported. Vaccination is critical for controlling the spread of BTV. In the last years, subunit vaccines, viral vector vaccines and reverse genetic-based vaccines have emerged as new alternatives to conventional ones. In this study, we developed an experimental subunit vaccine against BTV4, with the benefit of targeting the recombinant protein to antigen-presenting cells. The VP2 protein from an Argentine BTV4 isolate was expressed alone or fused to the antigen presenting cell homing (APCH) molecule, in the baculovirus insect cell expression system. The immunogenicity of both proteins was evaluated in guinea pigs and cattle. Titers of specific neutralizing antibodies in guinea pigs and cattle immunized with VP2 or APCH-VP2 were high and similar to those induced by a conventional inactivated vaccine. The immunogenicity of recombinant proteins was further studied in the IFNAR(-/-) mouse model where the fusion of VP2 to APCH enhanced the cellular immune response and the neutralizing activity induced by VP2.
蓝舌病病毒（BTV）是家养和野生反刍动物蓝舌病（BT）的病原体，在全球范围内均有分布。迄今为止，已鉴定出27种血清型，并有多次疫情报告。疫苗接种对于控制BTV的传播至关重要。近年来，亚单位疫苗、病毒载体疫苗和基于反向遗传学的疫苗已成为传统疫苗的新替代方案。在本研究中，我们开发了一种针对BTV4的实验性亚单位疫苗，其优势在于将重组蛋白靶向抗原呈递细胞。来自阿根廷BTV4分离株的VP2蛋白在杆状病毒昆虫细胞表达系统中单独表达或与抗原呈递细胞归巢（APCH）分子融合表达。在豚鼠和牛中评估了这两种蛋白的免疫原性。用VP2或APCH-VP2免疫的豚鼠和牛中特异性中和抗体的滴度很高，与传统灭活疫苗诱导的滴度相似。在IFNAR（-/-）小鼠模型中进一步研究了重组蛋白的免疫原性，其中VP2与APCH的融合增强了细胞免疫反应以及VP2诱导的中和活性。
