Power U F, Plotnicky-Gilquin H, Huss T, Robert A, Trudel M, Ståhl S, Uhlén M, Nguyen T N, Binz H
Centre d'Immunologie Pierre Fabre, Saint-Julien-en-Genevois, France.
Virology. 1997 Apr 14;230(2):155-66. doi: 10.1006/viro.1997.8465.
A subunit approach to the development of a respiratory syncytial virus (RSV) vaccine was investigated. It involved the production, in Escherichia coli, of an RSV (Long) G protein fragment (G2Na) as a C-terminal fusion partner to an albumin binding region (BB) of streptococcal protein G. G2Na incorporated amino acid residues 130-230 and was specifically recognized by murine anti-RSV-A polyclonal serum. In mice, intraperitoneal immunization with BBG2Na induced high anti-RSV-A serum ELISA titers and low to moderate neutralization activity. The immune response induced by BBG2Na demonstrated a potent protective efficacy against upper and lower respiratory tract RSV-A infection. The immunogenicity and protective efficacy of BBG2Na was maintained for at least 47 and 48 weeks, respectively, and was as potent and durable as live RSV-A administered in a similar fashion. Intramuscular immunization of cotton rats with BBG2Na protected lungs from both homologous and heterologous virus challenge. In contrast to mice, however, cotton rat nasal tracts were not protected after BBG2Na immunization. Consistent with antibody-mediated protection, virus was cleared within 24 hr from the lungs of BBG2Na-immunized mice. The anti-RSV-A antibodies induced in mice were exclusively of the IgG1 isotype and were detected in the serum, lungs, and nasal tracts. Passive transfer of these antibodies prevented acute, and eliminated chronic, RSV-A lung infection in normal and immunodeficient mice, respectively, confirming that such antibodies are important and sufficient for BBG2Na-induced pulmonary protection. Our results clearly demonstrate that BBG2Na contains an important immunogenic domain of the RSV G protein. The prokaryotic origin of this protein indicates that glycosylation of the RSV G protein is not necessary for protective efficacy. Thus, BBG2Na has potential as an RSV subunit vaccine.
研究了一种用于开发呼吸道合胞病毒（RSV）疫苗的亚单位方法。该方法涉及在大肠杆菌中生产RSV（Long株）G蛋白片段（G2Na），作为与链球菌蛋白G的白蛋白结合区域（BB）的C端融合伴侣。G2Na包含氨基酸残基130 - 230，能被鼠抗RSV - A多克隆血清特异性识别。在小鼠中，用BBG2Na进行腹腔免疫诱导了高抗RSV - A血清ELISA滴度和低至中度的中和活性。BBG2Na诱导的免疫反应对上下呼吸道RSV - A感染显示出强大的保护效力。BBG2Na的免疫原性和保护效力分别维持了至少47周和48周，并且与以类似方式接种的活RSV - A一样有效且持久。用BBG2Na对棉鼠进行肌肉注射免疫可保护肺部免受同源和异源病毒攻击。然而，与小鼠不同的是，BBG2Na免疫后棉鼠的鼻腔未得到保护。与抗体介导的保护一致，病毒在24小时内从BBG2Na免疫小鼠的肺部清除。在小鼠中诱导产生的抗RSV - A抗体仅为IgG1同种型，并且在血清、肺部和鼻腔中均可检测到。这些抗体的被动转移分别预防正常小鼠和免疫缺陷小鼠的急性RSV - A肺部感染并消除慢性感染，证实此类抗体对于BBG2Na诱导的肺部保护是重要且充分的。我们的结果清楚地表明，BBG2Na包含RSV G蛋白的一个重要免疫原性结构域。该蛋白的原核来源表明RSV G蛋白的糖基化对于保护效力并非必需。因此，BBG2Na作为RSV亚单位疫苗具有潜力。
