TITLE OF THE INVENTION
Method for quality control of an attenuated
varicella live vaccine
BACKGROUND OF THE INVENTION
Field of the Invention
The present invention relates to a method for
quality control of an attenuated varicella live vaccine.
More particularly, the present invention relates to a
method for quality control of an attenuated varicella
live vaccine, which comprises subjecting the genomic
DNA of a sample varicella vaccine virus to sequence
analysis and confirming that the genomic DNA of the
sample varicella vaccine virus conserves the specific
nucleotides without suffering mutation. By the use of
the method of the present invention, it has become pos-
sible to determine very accurately the qualification of
an attenuated varicella virus as an active ingredient
of an attenuated varicella live vaccine and, conse-
quently, to conduct an exact quality control of the
vaccines.
Prior Art
As is well known, attenuated varicella live vac-
cines used today are produced from a seed strain of
varicella virus which is derived from the attenuated
varicella virus Oka strain (see Examined Japanese Pat-
ent Application Publication No. 53-41202 and U.S. Pat-
ent No. 3,985,615), and the attenuated live vaccines
are used widely throughout the world (Requirements for
Varicella Vaccine (Live) Adopted 1984; Revised 1993:
WHO Technical Report Series, No. 848, pp. 22-38, 1994).
To ensure the safety and effectiveness of the vaccine,
the number of passages of a virus used for producing
the vaccine is restricted under the control of a seed
lot system, taking into consideration the potential ge-
netic mutation which is likely to occur during the pas-
sage. That is, the manufacturers are under an obliga-
tion to produce varicella vaccines only from the virus
derived from the approved seed virus for the live vari-
cella vaccine, wherein the number of passages of the
virus is not more than 10 as counted from the approved
seed virus which is counted as 0 passage. In other
words, the quality control and quality assurance of the
attenuated varicella live vaccine rely upon the ful-
fillment of the seed lot system by the manufacturers,
and such a method for the quality control and quality
assurance is not a method which can be traced and ana-
lyzed by a person skilled in the art.
Further, from the viewpoint of epidemiology which
involves a tracing of the effects of the varicella vac-
cine and a post-market surveillance (PMS), the vi-
rological difference between the fresh wild-type
strains isolated from the naturally infected varicella
patients and the vaccine virus strains derived from the
above-mentioned Oka strain needs to be determined, and
various analyses, such as those utilizing immunological
techniques and genetic engineering techniques, have
been attempted for determination of the virological
difference. For example, the following analyses have
been reported: the difference in DNA sequence between
the various VZV strains (Journal of Virology, 59, 660-
668, 1986; and