Murthy Ambika Mosale Venkatesh, Ni Yanyan, Meng Xiangjin, Zhang Chenming
Department of Biological Systems Engineering, Virginia Tech, Blacksburg, VA 24061, USA.
Center for Molecular Medicine and Infectious Disease, Department of Biomedical Sciences & Pathobiology, College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060, USA.
Int J Mol Sci. 2015 Apr 14;16(4):8382-96. doi: 10.3390/ijms16048382.
Porcine reproductive and respiratory syndrome (PRRS) is the most significant infectious disease currently affecting the swine industry worldwide. Several inactivated and modified live vaccines (MLV) have been developed to curb PRRSV infections. However, the efficacy and safety of these vaccines are unsatisfactory, and hence, there is a strong demand for the development of new PRRS universal vaccines. Virus-like particle (VLP)-based vaccines are gaining increasing acceptance compared to subunit vaccines, as they present the antigens in a more veritable conformation and are readily recognized by the immune system. Hepatitis B virus core antigen (HBcAg) has been successfully used as a carrier for more than 100 viral sequences. In this study, hybrid HBcAg VLPs were generated by fusion of the conserved protective epitopes of PRRSV and expressed in E. coli. An optimized purification protocol was developed to obtain hybrid HBcAg VLP protein from the inclusion bodies. This hybrid HBcAg VLP protein self-assembled to 23-nm VLPs that were shown to block virus infection of susceptible cells when tested on MARC 145 cells. Together with the safety of non-infectious and non-replicable VLPs and the low cost of production through E. coli fermentation, this hybrid VLP could be a promising vaccine candidate for PRRS.
猪繁殖与呼吸综合征(PRRS)是目前影响全球养猪业的最重要的传染病。已经开发了几种灭活疫苗和改良活疫苗(MLV)来抑制PRRSV感染。然而,这些疫苗的有效性和安全性并不理想,因此,对开发新的PRRS通用疫苗有强烈需求。与亚单位疫苗相比,基于病毒样颗粒(VLP)的疫苗越来越受到认可,因为它们以更真实的构象呈现抗原,并且易于被免疫系统识别。乙型肝炎病毒核心抗原(HBcAg)已成功用作100多种病毒序列的载体。在本研究中,通过融合PRRSV的保守保护性表位产生杂交HBcAg VLP,并在大肠杆菌中表达。开发了一种优化的纯化方案,以从包涵体中获得杂交HBcAg VLP蛋白。这种杂交HBcAg VLP蛋白自组装成23纳米的VLP,在MARC 145细胞上测试时显示可阻断易感细胞的病毒感染。连同非感染性和不可复制的VLP的安全性以及通过大肠杆菌发酵的低成本生产,这种杂交VLP可能是一种有前途的PRRS疫苗候选物。