Laboratory of Viral Infection I, Kitasato Institute for Life Sciences, Kitasato University, Shirokane 5-9-1, Minato-ku, Tokyo 108-8641, Japan.
Vaccine. 2011 Feb 4;29(7):1481-90. doi: 10.1016/j.vaccine.2010.12.028. Epub 2010 Dec 24.
Respiratory syncytial virus (RSV) is the most common cause of respiratory infection in infants, and no vaccine is available. In this report, recombinant AIK-C measles vaccines, expressing the RSV G or F protein of subgroup A (MVAIK/RSV/G or F), were investigated as a RSV vaccine candidate. MVAIK/RSV/G or F had the original ts phenotype and expressed RSV/G or F protein. Cross-reactive neutralizing antibodies against RSV subgroups A and B were detected in cotton rats immunized intramuscularly with MVAIK/RSV/F but not MVAIK/RSV/G. In cotton rats infected with RSV, RSV was recovered and lung histopathological finding was compatible with interstitial pneumonia, demonstrating thickening of alveolar walls and infiltration of mononuclear cells. When cotton rats immunized with MVAIK/RSV/F were challenged with homologous RSV subgroup A, no infectious RSV was recovered and very mild inflammation was noted without RSV antigen expression. When they were challenged with subgroup B, protective efficacy decreased. When cotton rats immunized with MVAIK/RSV/G were challenged with RSV subgroup A, low levels of infectious virus were recovered from lung. When challenged with subgroup B, no protective effects was demonstrated, demonstrating large amounts of RSV antigen in bronchial-epithelial cells. MVAIK/RSV/F is promising candidate and protective effects should be confirmed in monkey model.
呼吸道合胞病毒(RSV)是婴儿呼吸道感染最常见的原因,目前尚无可用的疫苗。在本报告中,研究了表达 A 亚群 RSV G 或 F 蛋白的重组 AIK-C 麻疹疫苗(MVAIK/RSV/G 或 F)作为 RSV 疫苗候选物。MVAIK/RSV/F 具有原始 ts 表型并表达 RSV/G 或 F 蛋白。在经肌肉内免疫的棉鼠中检测到针对 RSV 亚群 A 和 B 的交叉反应性中和抗体,但在 MVAIK/RSV/G 免疫的棉鼠中未检测到。在感染 RSV 的棉鼠中,回收了 RSV,肺组织病理学发现与间质性肺炎一致,显示肺泡壁增厚和单核细胞浸润。当用 MVAIK/RSV/F 免疫的棉鼠用同源 RSV 亚群 A 进行攻毒时,未回收感染性 RSV,仅观察到轻微炎症,且无 RSV 抗原表达。当用亚群 B 进行攻毒时,保护效力降低。当用 MVAIK/RSV/G 免疫的棉鼠用 RSV 亚群 A 进行攻毒时,从肺中回收低水平的感染性病毒。当用亚群 B 进行攻毒时,未显示出保护作用,支气管上皮细胞中存在大量 RSV 抗原。MVAIK/RSV/F 是一种很有前途的候选疫苗,其保护效果应在猴模型中得到证实。