Live attenuated vaccines based on cp45 hpiv-3 strain and method to

Abstract

The present invention is based upon correlation of two attenuating lesions of the cp45 strain to specific genetic defects in the viral genome of cp45. Specifically, it is now understood that a significant level of attenuation of cp45 giving rise to its temperature-sensitive and cold-adapted phenotypes is directly associated with mutation of the large, or L, gene of cp45 relative to the corresponding gene in the wild-type JS strain. Moreover, it is further understood that a second attenuating lesion exits independent of the temperature-sensitive lesion, and is directly associated with mutation of the hemagglutinin-neuraminidase gene, or HN gene, of cp45 relative to the corresponding gene in the wild-type HPIV-3 (JS) strain. The correlation of these two attenuating lesions of cp45 to specific genes enables several practical applications. It is now possible to create vaccines directed at other wild-type HPIV-3 viruses and, additionally, vaccines directed at target viruses other than HPIV-3 using genetic engineering techniques. For example, the mutated L and/or HN genes of cp45 can be incorporated into the viral genome of a target virus. Alternatively, the genes of the target virus which encode its surface antigens can be incorporated into the viral genome of cp45. Moreover, it is possible to determine whether an HPIV-3 strain or a hybrid virus strain made by the methods disclosed herein is attenuated by confirming the presence or absence of mutations in its L and/or HN genes.