Pre-clinical Vaccine Development for Respiratory Viruses

人类副粘病毒和肺炎病毒是分布广泛的病原体，造成相当大的疾病负担。副流感病毒14型(PIV14)是高度传染性的人类病原体，其中PIV3最常导致新生儿、老年人和免疫功能低下的人患上严重的呼吸道疾病。基于工程PIV3F融合稳定三聚体的冷冻电子显微镜结构，我们在四种PIV融合(F)糖蛋白中的每一种都引入了与我们之前公布的修饰不同的额外突变，以进一步稳定它们的亚稳灌流状态。候选疫苗能够诱导小鼠PIV类型特异性反应，与其他PIV几乎没有交叉中和作用。我们现在正在评估候选疫苗在非人类灵长类动物(NHP)中的中和反应。

Human paramyxoviruses and pneumoviruses are widespread pathogens, cause considerable disease burden. Parainfluenza virus types 14 (PIV14) are highly infectious human pathogens, of which PIV3 is most commonly responsible for severe respiratory illness in newborns, elderly, and immunocompromised individuals. Based on a cryoelectron microscopy structure of an engineered PIV3 F prefusion-stabilized trimer, we engineered in additional mutations different from our previous published modifications in each of the four PIV fusion (F) glycoproteins to further stabilize their metastable prefusion states. The vaccine candidates were able to elicit murine PIV type-specific response, with little cross-neutralization of other PIVs. We are now in the process of evaluating the neutralization responses of the vaccine candidates in nonhuman primates (NHPs).