Murphy B R, Sotnikov A, Paradiso P R, Hildreth S W, Jenson A B, Baggs R B, Lawrence L, Zubak J J, Chanock R M, Beeler J A
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Vaccine. 1989 Dec;7(6):533-40. doi: 10.1016/0264-410x(89)90278-8.
A formalin-inactivated respiratory syncytial virus (RSV) vaccine tested 22 years ago failed to protect infant vaccinees against RSV infection or disease. Instead, lower respiratory tract disease was enhanced during subsequent infection by RSV. Enhancement of pulmonary pathology is also observed when cotton rats are immunized with formalin-inactivated RSV and subsequently infected with this virus. A major question that must be addressed for each new paramyxovirus vaccine is whether the immunogen possesses the capacity to potentiate disease. In the present study, we evaluated a newly developed purified F and G glycoprotein vaccine over a wide dosage range for immunogenicity, efficacy and capacity to potentiate pulmonary pathology in cotton rats. In addition, a formalin-inactivated RSV vaccine, which served as a positive control for enhancement of pulmonary pathology, was evaluated simultaneously. The results of these comparisons indicate that the purified F and G glycoprotein vaccine was highly immunogenic and was efficacious even in animals that developed low levels of serum-neutralizing antibodies. Furthermore, the F and G vaccine did not induce potentiation of pulmonary pathology. In contrast, formalin-inactivated RSV potentiated RSV pulmonary histopathology, but there was a sparing of potentiation at high and low doses. Both the formalin-inactivated RSV and purified F and G preparations induced a high level of serum antibodies capable of binding to purified F and G glycoproteins but both sets of antibodies had significantly reduced neutralizing activity. These results are encouraging because they suggest that purified paramyxovirus glycoproteins might be used safely as a vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)
22年前测试的一种福尔马林灭活呼吸道合胞病毒（RSV）疫苗未能保护接种疫苗的婴儿免受RSV感染或疾病侵害。相反，在随后RSV感染期间，下呼吸道疾病反而加重。在用福尔马林灭活的RSV免疫棉鼠并随后感染该病毒时，也观察到肺部病理变化加剧。对于每一种新的副粘病毒疫苗，必须解决的一个主要问题是免疫原是否具有增强疾病的能力。在本研究中，我们在广泛的剂量范围内评估了一种新开发的纯化F和G糖蛋白疫苗在棉鼠中的免疫原性、效力以及增强肺部病理变化的能力。此外，同时评估了一种福尔马林灭活的RSV疫苗，其作为增强肺部病理变化的阳性对照。这些比较结果表明，纯化的F和G糖蛋白疫苗具有高度免疫原性，即使在产生低水平血清中和抗体的动物中也有效。此外，F和G疫苗不会诱导肺部病理变化增强。相比之下，福尔马林灭活的RSV增强了RSV肺部组织病理学变化，但在高剂量和低剂量时增强作用有所减轻。福尔马林灭活的RSV和纯化的F及G制剂均诱导产生了能够结合纯化F和G糖蛋白的高水平血清抗体，但两组抗体的中和活性均显著降低。这些结果令人鼓舞，因为它们表明纯化的副粘病毒糖蛋白可能作为疫苗安全使用。（摘要截短至250字）
