Virology Department, Animal and Plant Health Agency, Woodham Lane, Addlestone, KT15 3NB, United Kingdom.
Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, United Kingdom.
Sci Rep. 2017 Oct 23;7(1):13743. doi: 10.1038/s41598-017-13915-x.
Subunit viral vaccines are typically not as efficient as live attenuated or inactivated vaccines at inducing protective immune responses. This paper describes an alternative 'biomimetic' technology; whereby viral antigens were formulated around a polymeric shell in a rationally arranged fashion with a surface glycoprotein coated on to the surface and non-structural antigen and adjuvant encapsulated. We evaluated this model using BVDV E2 and NS3 proteins formulated in poly-(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles adjuvanted with polyinosinic:polycytidylic acid (poly(I:C) as an adjuvant (Vaccine-NP). This Vaccine-NP was compared to ovalbumin and poly(I:C) formulated in a similar manner (Control-NP) and a commercial adjuvanted inactivated BVDV vaccine (IAV), all inoculated subcutaneously and boosted prior to BVDV-1 challenge. Significant virus-neutralizing activity, and E2 and NS3 specific antibodies were observed in both Vaccine-NP and IAV groups following the booster immunisation. IFN-γ responses were observed in ex vivo PBMC stimulated with E2 and NS3 proteins in both vaccinated groups. We observed that the protection afforded by the particulate vaccine was comparable to the licenced IAV formulation. In conclusion, the biomimetic particulates showed a promising immunogenicity and efficacy profile that may be improved by virtue of being a customisable mode of delivery.
亚单位病毒疫苗在诱导保护性免疫反应方面通常不如减毒活疫苗或灭活疫苗有效。本文介绍了一种替代的“仿生”技术;即用聚合壳合理排列的方式将病毒抗原包裹在其中,表面涂有糖蛋白,非结构抗原和佐剂被包裹在内。我们使用 BVDV E2 和 NS3 蛋白在聚(D,L-乳酸-共-乙醇酸)(PLGA)纳米颗粒中进行了评估,该纳米颗粒用多聚肌苷酸:多聚胞苷酸(poly(I:C))作为佐剂(疫苗-NP)进行佐剂。将疫苗-NP 与以类似方式配制的卵清蛋白和 poly(I:C)(对照-NP)以及商业佐剂灭活 BVDV 疫苗(IAV)进行比较,所有疫苗均皮下接种,并在 BVDV-1 攻毒前进行加强免疫。在加强免疫后,疫苗-NP 和 IAV 组均观察到显著的病毒中和活性以及 E2 和 NS3 特异性抗体。在两组接种疫苗的 PBMC 中,用 E2 和 NS3 蛋白进行体外刺激后观察到 IFN-γ 反应。我们观察到,颗粒疫苗提供的保护与许可的 IAV 制剂相当。总之,仿生颗粒表现出有希望的免疫原性和疗效谱,由于其是一种可定制的递药方式,因此可能会得到改善。