摘要 |
Two recently characterized live attenuated HPIV1 vaccine candidates, rHPIV1-CR84G/ ?170HNT553ALY942A and rHPIV1-CR84G/? 170HNT553AL? 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/ ?170HNT553ALY942A was less attenuated than rHPIV1-CR84G/ ?170HNT553AL ?1710-11. 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. |
申请人 |
THE GOVERNMENT OF THE UNITED STATES OF AMERICA, REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH A;BARTLETT, EMMALENE;COLLINS, PETER, L.;SKIADOPOULOS, MARIO, H.;MURPHY, BRIAN, R. |
发明人 |
BARTLETT, EMMALENE;COLLINS, PETER, L.;SKIADOPOULOS, MARIO, H.;MURPHY, BRIAN, R. |