Saint Louis University

Robert B Belshe

Ranjit Ray

Frances K Newman

The present invention relates to isolated, attenuated viral strains of human parainfluenza virus 2 (HPIV-2), which are useful in live vaccine preparations. These strains exhibit a temperature sensitive and cold adapted phenotype useful for stimulating a protective immune response in an inoculated mammal without producing severe symptoms.

Temperature-sensitive and cold-adapted human parainfluenza virus type 2 (HPIV-2) and vaccines based on such virus

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.

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

The present invention is based upon the observation that the temperature sensitive phenotype of the cp45 strain of HPIV-3 correlates to a mutation in the large, or L, gene of cp45 relative to the corresponding gene in the wild-type strain. This correlation enables new vaccines directed at viruses other than HPIV-3 by combining, through genetic engineering methods, the region of the cp45 viral genome which encodes proteins responsible for replication and internal structure with the region of the genome of the target virus which encodes proteins responsible for attachment, penetration and release of the virus and virus progeny, respectfully. Moreover, it is possible to determine whether HPIV-3 or a cp45-hybrid virus is attenuated by confirming the presence or absence of mutations in its L gene.

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St. Louis, MO, United States of America

Robert B Belshe