Biomedical Research Center, Qatar University, 2713, Doha, Qatar.
College of Health Sciences, Qatar University, 2713, Doha, Qatar.
Eur J Clin Microbiol Infect Dis. 2018 Oct;37(10):1817-1827. doi: 10.1007/s10096-018-3289-4. Epub 2018 Jun 6.
Respiratory syncytial virus continues to pose a serious threat to the pediatric populations worldwide. With a genomic makeup of 15,200 nucleotides, the virus encodes for 11 proteins serving as envelope spikes, inner envelope proteins, and non-structural and ribonucleocapsid complexes. The fusion (F) and attachment (G) surface glycoproteins are the key targets for neutralizing antibodies. The highly variable G with altered glycosylations and the conformational alternations of F create challenges for vaccine development. The metastable F protein is responsible for RSV-host cell fusion and thus infectivity. Novel antigenic sites were identified on this form following its stabilization and solving its crystal structure. Importantly, site ø displays neutralizing activity exceeding those of post-F-specific and shared antigenic sites, such as site II which is the target for Palivizumab therapeutic antibody. Induction of high neutralizing antibody responses by pre-F immunization in animal models promoted it as a major vaccine candidate. Since RSV infection is more serious at age extremities and in individuals with undermining health conditions, vaccines are being developed to target these populations. Infants below three months of age have a suppressive immune system, making vaccines' immunogenicity weak. Therefore, a suggested strategy to protect newborns from RSV infection would be through passive immunity of maternal antibodies. Hence, pregnant women at their third trimester have been selected as an ideal target for vaccination with RSV pre-F vaccine. This review summarizes the different modes of RSV pathogenesis and host's immune response to the infection, and illustrates on the latest updates of vaccine development and vaccination approaches.
呼吸道合胞病毒（RSV）仍然对全球儿科人群构成严重威胁。该病毒的基因组由 15200 个核苷酸组成，编码 11 种蛋白，作为包膜刺突、内包膜蛋白、非结构和核衣壳复合物。融合（F）和附着（G）表面糖蛋白是中和抗体的关键靶标。高度可变的 G 具有改变的糖基化和 F 的构象改变，这给疫苗开发带来了挑战。不稳定的 F 蛋白负责 RSV-宿主细胞融合，从而具有感染性。在这种形式下，新的抗原表位在其稳定和解决晶体结构后被确定。重要的是，位点 ø 显示出超过 F 特异性和共享抗原位点（如 II 位点，是 Palivizumab 治疗性抗体的靶标）的中和活性。在动物模型中通过 pre-F 免疫诱导高中和抗体反应，促进了它作为主要疫苗候选物的地位。由于 RSV 感染在年龄极端和健康状况不佳的个体中更为严重，因此正在开发针对这些人群的疫苗。三个月以下的婴儿免疫系统受到抑制，使疫苗的免疫原性减弱。因此，保护新生儿免受 RSV 感染的一种建议策略是通过母体抗体的被动免疫。因此，已经选择妊娠晚期的孕妇作为 RSV pre-F 疫苗接种的理想目标。本综述总结了 RSV 发病机制和宿主对感染的免疫反应的不同模式，并说明了疫苗开发和接种方法的最新进展。
