Multicellular living organisms and unmodified parts thereof and – Method of using a transgenic nonhuman animal in an in vivo...
Patent
1995-11-15
1999-11-16
Stanton, Brian R.
Multicellular living organisms and unmodified parts thereof and
Method of using a transgenic nonhuman animal in an in vivo...
800 18, 800 9, 435455, 424 921, C12N 500, C12N 1500, C12N 1509, C12N 1563
Patent
active
059861711
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a method of examining the neurovirulence of a polio virus by inoculating a polio virus into the spinal cord of a transgenic, non-primate vertebrate animal with a gene for a polio virus receptor introduced therein.
BACKGROUND OF THE INVENTION
Poliomyelitis is a disease in the human central nervous system caused by a polio virus. The polio virus is divided into 3 serotypes i.e. types 1, 2 and 3, and it is considered that there are a variety of naturally occurring strains having weak (attenuated virus strains) to strong (virulent virus strains) levels of neurovirulence to which the primates only are sensitive.
Natural infection and prevalence of polio have occurred exclusively in the human being since ancient times as an infectious disease. A large number of humans still become infected with polio every year in developing countries. Hence, the eradication of polio in the near future is a task of the human being, and it is expected that a live polio vaccine can be the most effective weapon to solve this problem.
Although an attenuated polio virus has been produced and used as attenuated oral polio vaccine, the attenuated polio viruses may be dangerous for the possible reversion of pathogenicity (paralysis-based neurovirulence) in persons administered or in contact with it. Hence, there is a need for a safe and effective polio vaccine which is free of such pathogenicity. To produce such polio vaccine, consistency tests, particularly tests for neurovirulence of vaccine virus in monkeys, have been indispensable test.
Neurovirulence tests using monkeys, carried out worldwide at present, involve inoculating a predetermined amount of polio virus into the spinal cord of a monkey where the frequency of occurrence of paralysis and the histopathological changes in the central nervous system are clinically observed and numerically expressed in terms of "lesion score". In these prevailing tests for neurovirulence of attenuated polio viruses, a large number of monkeys such as cynomolgus monkeys are used.
However, these neurovirulence tests using monkeys suffer from the following disadvantages: (1) the price of the monkey is too high compared with conventional experimental animals; (2) a person handling the monkey is in the danger of infection with a pathogenic virus from the monkey; (3) the supply of the monkey declines for the protection of wild animals; and (4) wild monkeys are not homogeneous in genetic characteristics, resulting in data fluctuations even with the same sample (scattering results are inevitable).
In spite of these disadvantages, mice and rats cannot be used because such animals other than primates are not sensitive to the polio virus as described above.
SUMMARY OF THE INVENTION
The object of the present invention is to provide a method of examining neurovirulence, which comprises using transgenic non-primate vertebrate animals sensitive to polio virus in simple procedures, thus giving results correlated well with those of the conventional neurovirulence test using monkeys.
As a result of their eager research, the present inventors successfully developed a polio-sensitive test method which gives results correlated well with those of the conventional monkey neurovirulence test by inoculating a polio virus into the spinal cord of a transgenic non-primate vertebrate animal with a gene for a polio virus receptor introduced therein.
That is, the present invention is a method of examining the neurovirulence of a polio vaccine, which comprises inoculating a polio virus into the spinal cord of a transgenic non-primate vertebrate animal with a gene for a polio virus receptor introduced therein. Examples of transgenic non-primate vertebrate animals are transgenic mouse, transgenic rat, transgenic guinea pig and transgenic hamster. Examples of polio vaccines are attenuated strains from type 1, 2 or 3 of polio virus.
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, the present invention is described in detail.
The transgenic non-primate vertebrate an
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Abe Shinobu
Hashizume So
Koike Satoshi
Nomoto Akio
Nomura Tatsuji
Central Institute for Experimental Animals
Japan Poliomyelitis Research Institute
Martin Jill D.
Stanton Brian R.
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