Gershwin L J, Schelegle E S, Gunther R A, Anderson M L, Woolums A R, Larochelle D R, Boyle G A, Friebertshauser K E, Singer R S
Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis 95616, USA.
Vaccine. 1998 Jul;16(11-12):1225-36. doi: 10.1016/s0264-410x(98)80123-0.
A critical issue has been the observation that vaccination of children with a formalin-inactivated respiratory syncytial virus (RSV) vaccine is associated with disease enhancement. We have taken advantage of bovine RSV and our experience with this disease in calves to develop a natural model that parallels human disease. Using formalin-inactivated bovine RSV vaccine calves were either sham-vaccinated/infected, vaccinated/infected, or vaccinated/sham-infected and their clinical signs, pulmonary function, and histological lung lesions quantitatively scored. Interestingly there was significantly greater disease in vaccinated/infected calves and histological lesions in calves were similar to those of affected children. Finally, we note that vaccination did not induce neutralizing antibodies, but IgG antibodies were detected by ELISA. Our model of RSV enhanced disease is important because it provides quantifiable evidence of disease severity that can be applied to evaluate the mechanisms of immunopathology and the safety of candidate RSV vaccines.
一个关键问题是观察到用福尔马林灭活的呼吸道合胞病毒（RSV）疫苗给儿童接种与疾病加重有关。我们利用牛RSV以及我们在犊牛中对这种疾病的经验，开发了一种与人类疾病相似的自然模型。使用福尔马林灭活的牛RSV疫苗，将犊牛分为假接种/感染组、接种/感染组或接种/假感染组，并对它们的临床症状、肺功能和肺部组织学病变进行定量评分。有趣的是，接种/感染组的犊牛疾病明显更严重，且犊牛的组织学病变与患病儿童的相似。最后，我们注意到接种疫苗并未诱导中和抗体，但通过ELISA检测到了IgG抗体。我们的RSV疾病加重模型很重要，因为它提供了可量化的疾病严重程度证据，可用于评估免疫病理学机制和候选RSV疫苗的安全性。
