Department of Microbiology and Immunology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, 107 Wiggins Road, S7N 5E5, Canada; Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, Saskatoon, Saskatchewan, 120 Veterinary Road, S7N 5E3, Canada.
Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, Saskatoon, Saskatchewan, 120 Veterinary Road, S7N 5E3, Canada.
Antiviral Res. 2019 Nov;171:104594. doi: 10.1016/j.antiviral.2019.104594. Epub 2019 Aug 27.
Respiratory syncytial virus (RSV) is responsible for a large proportion of acute lower respiratory tract infections, specifically in children. Pneumonia virus of mice (PVM) causes similar lung pathology and clinical disease in rodents, and is therefore an appropriate model of RSV infection. Previously, we demonstrated that a single intranasal dose of P-I-P, a novel immunomodulator composed of the toll-like receptor 3 agonist poly(I:C), an innate defense regulator peptide and a polyphosphazene, confers protection in Balb/c mice for up to 3 days from lethal PVM-15 infection. In the present study a dual intranasal treatment with P-I-P was shown to extend the duration of the protection conferred by P-I-P from PVM-15 challenge. Balb/c mice treated twice with P-I-P showed higher survival rates and milder clinical signs when compared to animals that received a single P-I-P dose. While the mice treated with two consecutive doses of P-I-P experienced some weight loss, they all recovered. The dual P-I-P treatment mediated infiltration of several innate immune cells into the BALF and lung, including alveolar macrophages, neutrophils, and γδ T cells. Partial depletion of alveolar macrophages decreased survival rates and exacerbated clinical signs of mice subjected to the P-I-P dual treatment regime followed by PVM-15 challenge. This suggests that the alveolar macrophage is at least partially responsible for the protection elicited by this novel prophylactic treatment strategy.
呼吸道合胞病毒（RSV）是急性下呼吸道感染的主要病原体之一，尤其多见于儿童。鼠肺炎病毒（PVM）可引起啮齿动物类似的肺部病理和临床疾病，因此是 RSV 感染的合适模型。此前，我们证明了新型免疫调节剂 P-I-P（由 Toll 样受体 3 激动剂聚肌胞苷酸、先天防御调节剂肽和聚磷腈组成）的单次鼻腔内给药可在 Balb/c 小鼠中提供长达 3 天的保护，免受致死性 PVM-15 感染。在本研究中，双重鼻腔内 P-I-P 治疗可延长 P-I-P 从 PVM-15 攻击中获得的保护持续时间。与接受单次 P-I-P 剂量的动物相比，接受两次 P-I-P 治疗的 Balb/c 小鼠的存活率更高，临床症状更轻。尽管接受两次连续 P-I-P 治疗的小鼠体重略有下降，但它们均已恢复。双重 P-I-P 治疗可介导几种固有免疫细胞浸润 BALF 和肺部，包括肺泡巨噬细胞、中性粒细胞和γδ T 细胞。肺泡巨噬细胞的部分耗竭降低了存活率，并加重了接受 P-I-P 双重治疗方案后再接受 PVM-15 攻击的小鼠的临床症状。这表明肺泡巨噬细胞至少部分负责这种新型预防治疗策略引起的保护作用。
