The First Medical Center of Chinese PLA General Hospital, Beijing, China.
Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital, Beijing, China.
J Med Virol. 2024 Jul;96(7):e29308. doi: 10.1002/jmv.29308.
Respiratory syncytial virus (RSV) remains the primary cause of lower respiratory tract infections, particularly in infants and the elderly. In this study, we employed reverse genetics to generate a chimeric influenza virus expressing neuraminidase-3F protein conjugate with three repeats of the RSV F protein protective epitope inserted into the NA gene of A/California/7/2009 ca (CA/AA ca), resulting in rFlu/RSV/NA-3F (hereafter, rFRN3). The expression of NA-3F protein was confirmed by Western blotting. The morphology and temperature-sensitive phenotype of rFRN3 were similar to CA/AA ca. Its immunogenicity and protective efficiency were evaluated in BALB/c mice and cotton rats. Intranasal administration of rFRN3 elicited robust humoral, cellular, and to some extent, mucosal immune responses. Compared to controls, rFRN3 protected animals from RSV infection, attenuated lung injury, and reduced viral titers in the nose and lungs post-RSV challenge. These results demonstrate that rFRN3 can trigger RSV-specific immune responses and thus exhibits potent protective efficacy. The "dual vaccine" approach of a cold-adapted influenza vector RSV vaccine will improve the prophylaxis of influenza and RSV infection. rFRN3 thus warrants further clinical investigations as a candidate RSV vaccine.
呼吸道合胞病毒（RSV）仍然是下呼吸道感染的主要原因，特别是在婴儿和老年人中。在这项研究中，我们使用反向遗传学技术构建了一种嵌合流感病毒，该病毒表达神经氨酸酶-3F 蛋白，其与 RSV F 蛋白保护性表位的三个重复插入到 A/加利福尼亚/7/2009 株（CA/AA ca）的 NA 基因中，导致 rFlu/RSV/NA-3F（以下简称 rFRN3）。Western blot 证实了 NA-3F 蛋白的表达。rFRN3 的形态和温度敏感表型与 CA/AA ca 相似。在 BALB/c 小鼠和棉鼠中评估了其免疫原性和保护效率。rFRN3 经鼻腔给药可引起强烈的体液、细胞和在一定程度上黏膜免疫反应。与对照组相比，rFRN3 可保护动物免受 RSV 感染，减轻肺损伤，并降低 RSV 攻击后鼻腔和肺部的病毒滴度。这些结果表明，rFRN3 可以引发 RSV 特异性免疫反应，因此具有强大的保护效果。冷适应流感载体 RSV 疫苗的“双疫苗”方法将提高流感和 RSV 感染的预防效果。因此，rFRN3 作为 RSV 候选疫苗值得进一步临床研究。
