You Su-Hwa, Kim Taeseong, Choi Joo-Hyung, Park Gundo, Lee Kwang-Nyeong, Kim Byounghan, Lee Myoung-Heon, Kim Hyun-Soo, Kim Su-Mi, Park Jong-Hyeon
Foot-and-Mouth Disease Vaccine Research Center, Animal and Plant Quarantine Agency, 177 Hyeoksin 8-ro, Gimcheon-City, Gyeongsangbuk-do, Republic of Korea; Veterinary College of Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, Republic of Korea.
Foot-and-Mouth Disease Vaccine Research Center, Animal and Plant Quarantine Agency, 177 Hyeoksin 8-ro, Gimcheon-City, Gyeongsangbuk-do, Republic of Korea.
Antiviral Res. 2017 Jul;143:195-204. doi: 10.1016/j.antiviral.2017.04.009. Epub 2017 Apr 25.
Foot-and-mouth disease (FMD) is the cause of an economically devastating animal disease. With commercial inactivated FMD vaccines, the protection against FMD virus (FMDV) begins a minimum of 4 days post vaccination (dpv). Therefore, antiviral agents could be proposed for rapid protection and to reduce the spread of FMDV during outbreaks until vaccine-induced protective immunity occurs. In previous studies, we have developed two recombinant adenoviruses that simultaneously express porcine interferon-α and interferon-γ (Ad-porcine IFN-αγ) and multiple siRNAs that target the non-structural protein-regions of FMDV (Ad-3siRNA), and we have shown that the combination of the two antiviral agents (referred to here as Ad combination) induced robust protection against FMDV in pigs. In an attempt to provide complete protection against FMDV, we co-administered Ad combination and the FMD vaccine to mice and pigs. In the C57BL/6 mice model, we observed rapid and continuous protection against homologous FMDV challenge from 1 to 3 dpv-the period in which vaccine-mediated immunity is absent. In the pig experiments, we found that most of the pigs (five out of six) that received vaccine + Ad combination and were challenged with FMDV at 1 or 2 dpv were clinically protected from FMDV. In addition, most of the pigs that received vaccine + Ad combination and all pigs inoculated with the vaccine only were clinically protected from an FMDV challenge at 7 dpv. We believe that the antiviral agent ensures early protection from FMDV, and the vaccine participates in protection after 7 dpv. Therefore, we can say that the combination of the FMD vaccine and effective antiviral agents may offer both fast-acting and continuous protection against FMDV. In further studies, we plan to design coadministration of Ad combination and novel vaccines.
口蹄疫(FMD)是一种会造成巨大经济损失的动物疾病。对于商业化的口蹄疫灭活疫苗,接种疫苗后至少4天才能产生对口蹄疫病毒(FMDV)的保护作用。因此,可以考虑使用抗病毒药物来实现快速保护,并在疫情爆发期间减少FMDV的传播,直至疫苗诱导的保护性免疫产生。在之前的研究中,我们开发了两种重组腺病毒,一种同时表达猪α干扰素和γ干扰素(Ad-猪IFN-αγ),另一种表达靶向FMDV非结构蛋白区域的多个小干扰RNA(Ad-3siRNA),并且我们已经证明这两种抗病毒药物联合使用(在此称为Ad联合用药)能在猪体内诱导出对FMDV的强大保护作用。为了实现对FMDV的完全保护,我们将Ad联合用药与口蹄疫疫苗共同接种给小鼠和猪。在C57BL/6小鼠模型中,我们观察到在接种疫苗后1至3天(这段时间内不存在疫苗介导的免疫),小鼠能获得对同源FMDV攻击的快速且持续的保护。在猪的实验中,我们发现大多数在接种疫苗+Ad联合用药后于1或2天接种FMDV的猪(六只中有五只)在临床上受到保护,未感染FMDV。此外,大多数接种疫苗+Ad联合用药的猪以及所有仅接种疫苗的猪在7天接种FMDV后在临床上均受到保护。我们认为抗病毒药物能确保早期对FMDV的保护,而疫苗在7天后发挥保护作用。因此,可以说口蹄疫疫苗与有效的抗病毒药物联合使用可能会提供针对FMDV的快速起效且持续的保护。在进一步的研究中,我们计划设计Ad联合用药与新型疫苗的联合接种方案。