van den Hurk J V, van Drunen Littel-van den Hurk S
Veterinary Infectious Disease Organization, Saskatoon, Saskatchewan, Canada.
Vaccine. 1993;11(3):329-35. doi: 10.1016/0264-410x(93)90195-4.
Virus-neutralizing monoclonal antibodies specific for the hexon of haemorrhagic enteritis virus (HEV), a turkey adenovirus, were examined for their ability to confer passive protection against haemorrhagic enteritis (HE) in turkeys. A high dose of antibody prevented clinical disease and reduced virus replication in experimentally infected birds. This suggests that virus neutralization might be an important mechanism for protection against HE. Subsequently, the use of the hexon protein as a subunit vaccine was investigated by immunizing birds with affinity-purified HEV hexon. The birds were tested for the appearance of hexon-specific antibodies in their sera, for protection from clinical disease, and prevention of virus replication after challenge with virulent HEV (HEV-V). Regardless of whether birds were immunized with native or denatured hexon, high ELISA antibody titres were produced to each immunogen. A virus-neutralizing antibody response was induced by immunization with the native hexon but not by immunization with the denatured protein. All turkeys twice immunized with a dose of at least 1 microgram, and four out of five birds immunized with two doses of 0.3 micrograms of purified native hexon, were protected against virus-induced disease and virus replication. In contrast, birds inoculated with denatured hexon were not protected. These results demonstrate the importance of the native (trimeric) structure of the hexon protein for eliciting a protective immune response. The impact of these results on the development of a vaccine for HE in turkeys produced by recombinant DNA technology is discussed.
对出血性肠炎病毒(HEV,一种火鸡腺病毒)六邻体具有特异性的病毒中和单克隆抗体,被检测其在火鸡中赋予针对出血性肠炎(HE)的被动保护能力。高剂量抗体可预防临床疾病,并减少实验感染禽类中的病毒复制。这表明病毒中和可能是预防HE的重要机制。随后,通过用亲和纯化的HEV六邻体免疫禽类,研究了将六邻体蛋白用作亚单位疫苗的情况。检测这些禽类血清中六邻体特异性抗体的出现情况、对临床疾病的保护作用以及在用强毒HEV(HEV-V)攻击后对病毒复制的预防情况。无论禽类是用天然六邻体还是变性六邻体免疫,对每种免疫原均产生了高ELISA抗体滴度。用天然六邻体免疫诱导了病毒中和抗体反应,但用变性蛋白免疫则未诱导。所有用至少1微克剂量免疫两次的火鸡,以及五分之四用两剂0.3微克纯化天然六邻体免疫的禽类,均受到保护,免受病毒诱导的疾病和病毒复制。相比之下,接种变性六邻体的禽类未得到保护。这些结果证明了六邻体蛋白的天然(三聚体)结构对于引发保护性免疫反应的重要性。讨论了这些结果对通过重组DNA技术生产火鸡HE疫苗的影响。