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

A technology of human parainfluenza virus and virus strains, applied in the direction of microorganism-based methods, viruses, antiviral agents, etc., can solve problems such as difficulty in adapting to in vitro growth conditions, lowering temperature, etc.

Inactive Publication Date: 2001-09-26
SAINT LOUIS UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Despite their antigenic similarity, HPIV-2 is more difficult to adapt to in vitro growth conditions and reduced temperatures than HPIV-3

Method used

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] According to their phenotypic characteristics, three ts and ca clones, C3440, C3464 and C3490, were selected for evaluation in hamsters. Table 3 illustrates the ts and ca phenotypes of these selected clones and the wt parents of these HPIV-2 vaccine candidates. The newly weaned hamsters are deeply anesthetized and vaccinated intranasally with wt parental virus or a candidate vaccine. Table 4 shows the titer of the inoculum received by the hamster. The total amount of inoculum received by each animal is 0.1ml (0.05ml / nostril). To prevent cross-contamination, use a micropipette with aerosol-resistant pipette tip. Hamsters were vaccinated with a candidate vaccine or wt parental virus in groups of 20. Four hamsters in each group were euthanized at five time points (i.e., 1, 2, 3, 4, and 7 days after vaccination). Ten non-vaccinated animals (2 at each of the five time points) were euthanized as a control group. On the day of harvest, the lungs and turbinates of each animal were ...

Embodiment 2

[0034] Each clone evaluated in hamsters was also tested for genetic stability in vitro. We conducted a stress test on each clone. The method was to pass each clone into successive generations blindly, once a week for a total of four weeks, and the temperature was the allowable temperature (32°C), the intermediate allowable temperature (35°C), and Limit the temperature (39°C) to determine whether the virus reverts back to the wild-type phenotype under the selective pressure that is not conducive to the ts phenotype. Table 5 shows the results of the stress test. After each passage, the virus was titrated at 32°C to 39°C to detect ts phenotype changes. Each clone maintained its ts phenotype after serial passage at 39°C, indicating that they were genetically stable.

[0035]In addition to the stress test, we select plaques from each of the three cold-passage viruses to determine whether there is a mixture of virus phenotypes in the virus library. (Table 6) Each of the 10 subclones sel...

Embodiment 3

[0037] The three clones of SLU7255, C3464 (cp50), C3490 (cp51), and C3605 (cp63, a subclone of C3440), have become the most promising vaccine candidates. These three clones were evaluated in seronegative rhesus monkeys. Prepare a virus library for each clone and wt virus in Vero cells. Table 7 shows the titers of the libraries used in the following examples.

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Abstract

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.

Description

Background of the invention [0001] The present invention relates to an isolated attenuated virus strain of human parainfluenza virus type 2 (HPIV-2), which is useful in the preparation of live vaccines. These virus strains show a temperature-sensitive and cold-adapted phenotype, which is useful for stimulating a protective immune response in the vaccinated mammal without producing severe symptoms caused by the wild-type virus. [0002] Human parainfluenza virus types 1, 2, and 3 (HPIV) are important pathogens for infants and young children. HPIV usually causes otitis media, pharyngitis, and the common cold. These upper respiratory tract infections (URI) often occur and can be accompanied by lower respiratory tract infections (LRI), including croup, pneumonia, and bronchiolitis. The first infection in young children is accompanied by lower respiratory tract disease and often leads to hospitalization. As a group, parainfluenza virus is the second most common cause of hospital admiss...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/145C12N7/04A61K39/155A61K39/39A61P31/16C12N7/08C12R1/92
CPCA61K39/155C12N2760/18764C12N7/00A61K2039/5254C12N2760/18734A61K2039/543A61K39/12A61P31/16
Inventor R·B·贝尔希F·K·纽曼
Owner SAINT LOUIS UNIVERSITY
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