Mason P W, Chinsangaram J, Moraes M P, Mayr G A, Grubman M J
Foot-and-Mouth Disease Research Unit, Plum Island Animal Disease Center, Agricultural Research Service, USDA, Greenport, NY 11944, USA.
Dev Biol (Basel). 2003;114:79-88.
Although efficacious and safe, current vaccines for FMD suffer from drawbacks. Among these are that the immune response to the vaccine interferes with the ability to detect vaccinated animals that have subsequently become infected and could carry and shed the virus, creating an obstacle to re-instating disease-free status to countries/regions that vaccinate to control outbreaks. Multiple diagnostic tests are available to identify animals that have been infected with FMDV by detection of antibodies to viral non-structural proteins (NSP) that are present in low concentration in traditional vaccines and are poorly immunogenic in vaccine preparations. However, these tests are not 100% reliable. To circumvent this problem, we have developed a new generation of vaccines that express the "empty capsid" subunit of the virus, in the absence of one of the most immunogenic NSPs, 3Dpol. Here we describe delivery of the empty capsid subunits by recombinant replication-defective human adenovirus type 5 (Ad5). These Ad5-vectored empty capsid vaccines can protect pigs from FMDV challenge as early as 7 days post-vaccination. A second problem with current FMD vaccines is that they do not induce protective immunity quickly, a drawback that is likely to be shared by our Ad5-vectored empty capsid vaccine. To overcome this problem, we have developed a prophylactic antiviral treatment consisting of an Ad5 encoding porcine interferon alpha (pIFNalpha). Administration of Ad5-pIFNalpha protects swine from FMD as early as one day post-administration. The combination of this antiviral treatment and the empty capsid subunit vaccine should induce rapid and complete protection from FMD, and could overcome current diagnostic problems.
尽管目前的口蹄疫疫苗有效且安全，但仍存在缺点。其中之一是疫苗引发的免疫反应会干扰对已接种疫苗但随后感染并可能携带和传播病毒的动物的检测能力，这给已接种疫苗以控制疫情的国家/地区恢复无病状态带来了障碍。有多种诊断测试可用于通过检测针对病毒非结构蛋白（NSP）的抗体来识别感染了口蹄疫病毒的动物，这些蛋白在传统疫苗中浓度较低，且在疫苗制剂中的免疫原性较差。然而，这些测试并非100%可靠。为了解决这个问题，我们开发了新一代疫苗，该疫苗在缺少最具免疫原性的NSP之一3Dpol的情况下表达病毒的“空衣壳”亚基。在此我们描述了通过重组复制缺陷型人5型腺病毒（Ad5）递送空衣壳亚基。这些Ad5载体空衣壳疫苗可在接种疫苗后7天就保护猪免受口蹄疫病毒攻击。目前口蹄疫疫苗的另一个问题是它们不能快速诱导保护性免疫，我们的Ad5载体空衣壳疫苗可能也存在这一缺点。为克服这一问题，我们开发了一种预防性抗病毒治疗方法，由编码猪α干扰素（pIFNα）的Ad5组成。给予Ad5-pIFNα最早在给药后一天就可保护猪免受口蹄疫感染。这种抗病毒治疗与空衣壳亚基疫苗的组合应能诱导对口蹄疫的快速和完全保护，并可克服当前的诊断问题。
