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
Two recently characterized live attenuated HPIV1 vaccine candidates, rHPIV1-CR84G/170HNT553ALY942A and rHPIV1-CR84G/170HN-T553AL1710-11, 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° C.) and restrictive (37° C.) temperatures. The viruses grew slightly better at 37° C. than at 32° C., and rHPIV1-CR84G/170HNT553A-LY942A was less attenuated than rHPIV1-CR84G/170HNT553AL1710-11. 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.
展开▼