National Center for Immunization and Respiratory Diseases, Division of Viral Diseases, Gastroenteritis and Respiratory Viruses Laboratory Branch, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, United States of America.
College of Veterinary Medicine, Department of Infectious Disease, University of Georgia, Athens, Georgia, United States of America.
PLoS One. 2013 Dec 23;8(12):e83075. doi: 10.1371/journal.pone.0083075. eCollection 2013.
Respiratory syncytial virus (RSV) is a high priority target for vaccine development. One concern in RSV vaccine development is that a non-live virus vaccine would predispose for enhanced disease similar to that seen with the formalin inactivated RSV (FI-RSV) vaccine. Since a mAb specific to RSV G protein can reduce pulmonary inflammation and eosinophilia seen after RSV infection of FI-RSV vaccinated mice, we hypothesized that RSV G peptides that induce antibodies with similar reactivity may limit enhanced disease after subunit or other non-live RSV vaccines. In support of this hypothesis, we show that FI-RSV vaccinated mice administered RSV G peptide vaccines had a significant reduction in enhanced disease after RSV challenge. These data support the importance of RSV G during infection to RSV disease pathogenesis and suggest that use of appropriately designed G peptide vaccines to reduce the risk of enhanced disease with non-live RSV vaccines merits further study.
呼吸道合胞病毒 (RSV) 是疫苗开发的高度优先目标。在 RSV 疫苗开发中令人关注的是,非活病毒疫苗会导致类似于福尔马林灭活 RSV(FI-RSV)疫苗所见到的增强疾病。由于针对 RSV G 蛋白的 mAb 可减少 FI-RSV 接种小鼠 RSV 感染后的肺部炎症和嗜酸性粒细胞增多,我们假设诱导具有类似反应性抗体的 RSV G 肽可能会限制亚单位或其他非活 RSV 疫苗后的增强疾病。为了支持这一假设,我们表明,给予 RSV G 肽疫苗的 FI-RSV 接种小鼠在 RSV 攻击后增强疾病的严重程度显著降低。这些数据支持 RSV G 在感染过程中对 RSV 疾病发病机制的重要性,并表明使用适当设计的 G 肽疫苗来降低非活 RSV 疫苗增强疾病的风险值得进一步研究。