Cyr Sonya L, Jones Taff, Stoica-Popescu Ioana, Burt David, Ward Brian J
McGill Center for Tropical Diseases, Montreal General Hospital, Montreal, Quebec, Canada H3G IA4.
Vaccine. 2007 Apr 20;25(16):3228-32. doi: 10.1016/j.vaccine.2007.01.037. Epub 2007 Jan 22.
The protective efficacy of an intranasal (IN) Protollin-eRSV vaccine has recently been demonstrated in the RSV-susceptible BALB/c mouse model. Here, we report the safety, immunogenicity and efficacy of Protollin-eRSV vaccine in the relatively resistant C57Bl/6 mouse model. C57Bl/6 mice immunized IN with either two or three doses of Protollin-eRSV produced significant systemic and mucosal RSV-specific antibodies. Mice immunized with the Protollin vaccine displayed polarized Th1 responses with augmented IFNgamma/IL-5 ratios in RSV-restimulated lung and spleen cell preparations compared with animals that received antigen alone. The Protollin-eRSV immunized C57Bl/6 mice were fully protected against challenge without eosinophilic pulmonary pathology observed in the animals immunized with the formalin-inactivated RSV vaccine. This new model will permit us to dissect the respective roles of the TLR2 and TLR4 ligands contained in the vaccine using TLR knock-out animals established on the C57Bl/6 background.
鼻内(IN)Protollin-eRSV疫苗的保护效力最近已在对呼吸道合胞病毒(RSV)易感的BALB/c小鼠模型中得到证实。在此,我们报告Protollin-eRSV疫苗在相对抗性较强的C57Bl/6小鼠模型中的安全性、免疫原性和效力。用两剂或三剂Protollin-eRSV经鼻内免疫的C57Bl/6小鼠产生了显著的全身性和粘膜性RSV特异性抗体。与仅接受抗原的动物相比,用Protollin疫苗免疫的小鼠在RSV再刺激后的肺和脾细胞制剂中表现出极化的Th1反应,IFNγ/IL-5比值增加。经Protollin-eRSV免疫的C57Bl/6小鼠受到完全保护,免受攻击,在用福尔马林灭活的RSV疫苗免疫的动物中未观察到嗜酸性粒细胞性肺部病变。这个新模型将使我们能够利用在C57Bl/6背景上建立的TLR基因敲除动物来剖析疫苗中所含TLR2和TLR4配体的各自作用。