Centro de Investigación en Sanidad Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Madrid, Spain.
PLoS One. 2010 Apr 29;5(4):e10414. doi: 10.1371/journal.pone.0010414.
New vaccine designs are needed to control diseases associated with antigenically variable RNA viruses. Foot-and-mouth disease (FMD) is a highly contagious disease of livestock that inflicts severe economic losses. Although the current whole-virus chemically inactivated vaccine has proven effective, it has led to new outbreaks of FMD because of incomplete inactivation of the virus or the escape of infectious virus from vaccine production premises. We have previously shown that serial passages of FMD virus (FMDV) C-S8c1 at high multiplicity of infection in cell culture resulted in virus populations consisting of defective genomes that are infectious by complementation (termed C-S8p260).
Here we evaluate the immunogenicity of C-S8p260, first in a mouse model system to establish a proof of principle, and second, in swine, the natural host of FMDV C-S8c1. Mice were completely protected against a lethal challenge with FMDV C-S8c1, after vaccination with a single dose of C-S8p260. Pigs immunized with different C-S8p260 doses and challenged with FMDV C-S8c1 either did not develop any clinical signs or showed delayed and mild disease symptoms. C-S8p260 induced high titers of both FMDV-specific, neutralizing antibodies and activated FMDV-specific T cells in swine, that correlated with solid protection against FMDV.
The defective virus-based vaccine did not produce detectable levels of transmissible FMDV. Therefore, a segmented, replication-competent form of a virus, such as FMDV C-S8p260, can provide the basis of a new generation of attenuated antiviral vaccines with two safety barriers. The design can be extended to any viral pathogen that encodes trans-acting gene products, allowing complementation between replication-competent, defective forms.
需要新的疫苗设计来控制与抗原可变的 RNA 病毒相关的疾病。口蹄疫（FMD）是一种高度传染性的牲畜疾病，会造成严重的经济损失。尽管目前的全病毒化学灭活疫苗已被证明有效，但由于病毒不完全灭活或传染性病毒从疫苗生产场所逃逸，导致新的口蹄疫爆发。我们之前已经表明，在细胞培养中以高感染复数对 FMD 病毒（FMDV）C-S8c1 进行连续传代，会导致由缺陷基因组组成的病毒群体，这些基因组通过互补作用具有感染性（称为 C-S8p260）。
在这里，我们首先在小鼠模型系统中评估 C-S8p260 的免疫原性，以建立原理证明，其次在 FMDV C-S8c1 的天然宿主猪中进行评估。用 C-S8p260 进行单次接种后，小鼠完全免受致死性 FMDV C-S8c1 攻击的保护。用不同剂量的 C-S8p260 免疫的猪在受到 FMDV C-S8c1 攻击时，要么没有出现任何临床症状，要么表现出延迟和轻微的疾病症状。C-S8p260 在猪中诱导了高滴度的 FMDV 特异性中和抗体和激活的 FMDV 特异性 T 细胞，与对 FMDV 的有效保护相关。
缺陷病毒疫苗未产生可检测水平的可传播口蹄疫病毒。因此，具有两个安全屏障的病毒的分段、复制能力形式，例如 FMDV C-S8p260，可以为新一代减毒抗病毒疫苗提供基础。该设计可以扩展到任何编码反式作用基因产物的病毒病原体，允许复制能力缺陷形式之间的互补。
