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Pre-clinical Vaccine Development for Respiratory Viruses

Pre-clinical Vaccine Development for Respiratory Viruses
呼吸道病毒临床前疫苗开发
批准号:
10274170
负责人:
John Mascola
金额:
$274.8万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:

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中文摘要
翻译
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。
英文摘要
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).
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会议论文
Next Generation Development of Broadly Neutralizing HIV Antibodies for Prevention
HIV/AIDS Vaccine and Antibody Development
Pre-clinical Vaccine and Antibody Development for Coronavirus Disease 2019 (COVID-19)
Measurement of HIV Neutralization Using Quantitative Assays
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