Live attenuated Japanese encephalitis vaccine strain sa14-14-2 adapted to human diploid cell 2bs and its vaccine

Abstract

The invention provides an adaptive strain of a Japanese encephalitis vaccine strain SA14-14-2 in human diploid cells 2BS and a vaccine of the adaptive strain. The adaptive strain is characterized in that epidemic encephalitis b virus SA14-14-2 is inoculated to a human diploid cell and is subjected to continuous passage by virtue of different methods, so that the virus can propagate in the cell with favorable adaptability and stability, relatively high-titer viruses are obtained, and a three-level virus seed library of viruses is established; by virtue of measuring whole-genome sequence of the virus seed library, the whole-genome sequence thereof is obtained. Effectiveness and safety inspection is performed on the viruses, and the viruses conform to specified standards of Japanese encephalitis vaccines. The Japanese encephalitis strain is relatively high in virus titer, has safety conforming to specification, is favorable in immunogenicity and stable in heredity, conforms to requirements on safety and effectiveness of Japanese encephalitis strains in the third version (2010 edition) of Chinese Pharmacopoeia and is suitable for serving as a strain for producing encephalitis b vaccines.

Description

technical field [0001] The invention belongs to the field of virus vaccines, in particular to breeding highly attenuated Japanese encephalitis live vaccine strains with good immunogenicity by biological technology. The Japanese encephalitis live attenuated vaccine strain SA14-14-2 was inoculated into 2BS cells in a monolayer and suspension manner, and the virus titer was determined by the plaque method after passage to determine the optimal harvest time and inoculation volume of the virus. Select the three generations with higher virus titers to establish the original virus seed, the main generation virus seed and the working virus seed bank, and carry out sterility inspection, mycoplasma inspection, and immunogenicity inspection on the virus seed library virus in accordance with the three parts of the "Chinese Pharmacopoeia". The test of pathogenicity in rat brain, the test of subcutaneous infection into the brain, the test of ancestral passage in suckling mice, and the compr...

AI Technical Summary

Problems solved by technology

Disadvantages of purified murine and JE vaccines include: short duration of induction of protective immunity, requiring multiple doses; relatively high price per dose for most countries

However, both Vero cells and primary hamster kidney cells are animal-derived cells. The advantages of Vero cells are that their quality and exogenous factors can be highly controlled, their propagation speed is fast, their duration is long, and they are easy to standardize. The potential carcinogenicity risk of Vero cell DNA to vaccinators, so the residual content must be strictly controlled in the vaccine preparation process

The primary hamster kidney cells are derived from hamsters. The hamster population is not only difficult to control, but also requires relatively high production technology, and is easily contaminated by foreign substances such as bacteria, viruses, and parasites. Currently, China Chengdu Institute of Biological Products Co., Ltd. The live attenuated Japanese encephalitis vaccine produced uses SPF hamster kidney cells as the cell matrix for vaccine production, which can better solve the above-mentioned problem of exogenous factor contamination that people worry about, but increases the cost of the vaccine

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