首页> 外国专利> RECOMBINANT HUMAN PARAINFLUENZA TYPE 1 VIRUSES (HPIV1S) CONTAINING MUTATIONS IN OR DELETION OF THE C PROTEIN ARE ATTENUATED IN AFRICAN GREEN MONKEYS AND IN CILIATED HUMAN AIRWAY EPITHELIAL CELLS AND ARE POTENTIAL VACCINE CANDIDATES FOR HPIV1

RECOMBINANT HUMAN PARAINFLUENZA TYPE 1 VIRUSES (HPIV1S) CONTAINING MUTATIONS IN OR DELETION OF THE C PROTEIN ARE ATTENUATED IN AFRICAN GREEN MONKEYS AND IN CILIATED HUMAN AIRWAY EPITHELIAL CELLS AND ARE POTENTIAL VACCINE CANDIDATES FOR HPIV1

机译：在非洲绿色猴子和人肺气道上皮细胞中，含有突变或缺失C蛋白的重组人帕氏肺炎1型病毒（HPIV1S）减弱，并且是HPIV1的潜在疫苗候选物

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Two recently characterized live attenuated HPIV1 vaccine candidates, rHPIV1-CR84G/ Δ170HNT553ALY942A and rHPIV1-CR84G/Δ 170HNT553ALΔ 1710-11, which contain temperature sensitive (ts) attenuating (att) and non-ts att mutations, were evaluated in a Human Airway Epithelium (HAE) model culture system and in vivo in African Green monkeys (AGM). The vaccine candidates were highly restricted in growth in HAE at permissive (32 o C) and restrictive (37 o C) temperatures. The viruses grew slightly better at 37 o C than at 32 oC, and rHPIV1-CR84G/ Δ170HNT553ALY942A was less attenuated than rHPIV1-CR84G/ Δ170HNT553AL Δ1710-11. The level of replication in HAE correlated with that observed in African Green monkeys, suggesting that the HAE model is useful as a tool for pre-clinical evaluation of HPIV1 vaccines. A live attenuated HPIV1 vaccine candidate having a normal P/C gene structure of overlapping P and C open reading frames, but does not express any functional C protein, is found to highly attenuated in AGMs, and provides a significant immune response in AGMs.

机译：在人类呼吸道上皮细胞中评估了两种最近鉴定的减毒活HPIV1候选疫苗rHPIV1-CR84G /Δ170HNT553ALY942A和rHPIV1-CR84G /Δ170HNT553ALΔ1710-11 （HAE）模型培养系统和非洲绿猴（AGM）体内。在允许的温度（32 o C）和限制的温度（37 o C）下，候选疫苗的HAE生长受到严格限制。该病毒在37 o C时比在32 o C时生长略好，并且rHPIV1-CR84G /Δ170HNT553ALY942A的减毒程度小于rHPIV1-CR84G /Δ170HNT553ALΔ1710-11。 HAE中的复制水平与非洲绿猴中观察到的水平相关，这表明HAE模型可用作临床前评估HPIV1疫苗的工具。具有正常的P / C基因结构，重叠的P和C开放阅读框，但不表达任何功能性C蛋白的减毒活HPIV1候选疫苗在AGM中被高度减毒，并在AGM中提供了重要的免疫应答。

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公开/公告号WO2010003032A2

专利类型
公开/公告日2010-01-07

原文格式PDF
申请/专利权人 THE GOVERNMENT OF THE UNITED STATES OF AMERICA REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH AND HUMAN SERVICES;BARTLETT EMMALENE;COLLINS PETER L.;SKIADOPOULOS MARIO H.;MURPHY BRIAN R.;
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申请/专利号WO2009US49461
发明设计人 BARTLETT EMMALENE;COLLINS PETER L.;SKIADOPOULOS MARIO H.;MURPHY BRIAN R.;
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申请日2009-07-01
分类号C07K14/005;
国家 WO
入库时间 2022-08-21 18:40:18

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