Chinsangaram J, Mason P W, Grubman M J
USDA, ARS, NAA, Plum Island Animal Disease Center, Greenport, NY 11944, USA.
Vaccine. 1998 Oct;16(16):1516-22. doi: 10.1016/s0264-410x(98)00029-2.
Previously, we demonstrated that a genetically engineered variant of foot-and-mouth disease virus (FMDV) serotype A12 lacking the leader proteinase-coding region (A12-LLV2) was attenuated and induced an immune response that partially protected cattle from FMD. In this study, A12-LLV2 was tested in swine as a live or chemically inactivated vaccine. Animals vaccinated with chemically inactivated A12-LLV2 or wild-type (WT) virus in oil adjuvant developed high levels of neutralizing antibodies and were protected from FMD upon challenge. Animals vaccinated with live A12-LLV2 did not exhibit signs of FMD, did not spread virus to other animals, developed a neutralizing antibody response and antibodies to nonstructural protein 3D, and were partially protected from FMD. Animals given a similar dose of chemically inactivated A12-LLV2 in the absence of adjuvant developed a poor immune response and were not protected from FMD, indicating that limited replication was responsible for the improved immune response found in animals vaccinated with live A12-LLV2. The results demonstrate the potential of A12-LLV2 as a live-attenuated vaccine as well as a safe source of antigen for chemically inactivated vaccines.
此前,我们证明了一种基因工程改造的A型口蹄疫病毒(FMDV)血清型A12变体,其缺乏前导蛋白酶编码区(A12-LLV2),具有减毒作用,并能诱导产生免疫反应,可部分保护牛免受口蹄疫侵害。在本研究中,对A12-LLV2作为活疫苗或化学灭活疫苗在猪身上进行了测试。用化学灭活的A12-LLV2或野生型(WT)病毒与油佐剂一起接种的动物产生了高水平的中和抗体,并在受到攻击时受到口蹄疫保护。用活的A12-LLV2接种的动物未表现出口蹄疫症状,未将病毒传播给其他动物,产生了中和抗体反应以及针对非结构蛋白3D的抗体,并受到部分口蹄疫保护。在无佐剂情况下给予相似剂量化学灭活A12-LLV2的动物产生的免疫反应较差,未受到口蹄疫保护,这表明有限的复制是接种活A12-LLV2的动物免疫反应改善的原因。结果证明了A12-LLV2作为减毒活疫苗以及化学灭活疫苗安全抗原来源的潜力。