非洲猪瘟疫苗研究的困境和展望

非洲猪瘟（ASF）目前是生猪产业最重要的猪病。因为非洲猪瘟病毒（ASFV）本身的复杂性，以及和宿主相互作用的复杂性导致ASF已经被报道一百年了，还没有商业化疫苗。理想的ASF疫苗不仅要有好的免疫保护性，更重要的是其安全性，同时如果能区分野毒感染和疫苗接种，能在适合的高质量GMP车间进行稳定低价的生产，能用于不同物种就更好了。ASF灭活疫苗研制这条道路似乎不通；亚单位疫苗、DNA疫苗、病毒活载体疫苗的免疫保护能力不足；主要包含自然缺失、传代致弱、基因工程缺失的减毒活疫苗在免疫保护方面体现了非常大的优势，但是其潜在的持续感染风险，会造成猪只的副作用，包括皮肤溃烂、关节炎，导致神经系统、呼吸系统的损伤等问题非常值得警惕。复制缺陷单周期病毒能有效地解决减毒活疫苗的安全性问题，似乎是一个值得尝试的ASF疫苗研制方向，尽管存在难以确定缺失复制相关的基因，以及难以构建能高效表达缺失基因编码蛋白，且能让单周期病毒稳定大量生产的辅助细胞系。我国针对ASFV强毒的精准剔除策略，未注册非法弱毒苗造成临床严重损失，以及一些不使用疫苗但成功从国家层面净化ASF的案例，让我们认识到针对ASF基础研究的重要性。同时至少目前阶段，ASF的防控不一定要借助疫苗，更多的要做好生物安全管控和区域ASF净化。尽管ASF疫苗研制困难重重，但针对ASF理想型疫苗的研制也应该持续进行下去，未来可能作为ASF防控的一个突破点。

Dilemma and prospect of African swine fever vaccine research

African swine fever (ASF) is currently the most important swine disease for the pig industry. Due to the complexity of African swine fever virus (ASFV) and its interaction with the host, no commercial vaccine against ASF has been successfully developed since ASF was fi rstly reported 100 years ago. The ideal ASF vaccine should not only have good immune protection ability, but also its safety. It will be better if it can distinguish wild virus infection from vaccination, be produced stably and cheaply in a suitable high-quality GMP workshop, and be used in different species at the same time. The development of inactivated ASF vaccine seems impossible. The immune protection ability of subunit vaccine, DNA vaccine and live viral vector vaccine is not enough. The live attenuated vaccine including natural deletions, passage attenuated and genetic engineering deletions, shows great advantages in immune protection, but its potential risk of persistent infection will cause side effects on pigs, including skin ulceration and arthritis, resulting in damage to the nervous system and respiratory system, which is worthy of vigilance. Replication defective single cycle virus can effectively solve the safety problem of live attenuated vaccine. It seems to be a potential vaccine development direction worth trying, though it is difficult to determine the genes related to deletion of replication, and to construct helper cell lines that can efficiently express the protein encoded by the deleted gene and allow the stable and mass production of single cycle virus. China''s successful strategy of precise diagnostic and elimination strategy of wild type virulent ASFV, serious clinical losses caused by unregistered illegal attenuated vaccines, and some cases of successful eradication of ASF from the national level without using vaccines have made us realize the importance of basic research on ASF. At least at the present stage, the prevention and control of ASF does not have to rely on vaccines, but more on biosafety control and regional ASF eradication. Although there are many difficulties in the development of ASF vaccine, the development of ideal ASF vaccine should be continued, which may be a breakthrough point in the prevention and control of ASF in the future.