Application of PCR for Detection of Mycoplasma DNA and Pestivirus RNA in Human Live Viral Vaccines

Sasaki, Tsuguo; Harasawa, Ryô; Shintani, Miharu; Fujiwara, Hiroshi; Sasaki, Yukie; Horino, Atsuko; Kenri, Tsuyoshi; Asada, Kiyozo; Kato, Ikunosin; Chino, Fumitoshi

doi:10.1006/biol.1996.0052

Cited by 13 publications

(5 citation statements)

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“…As reported previously, many lots of human live viral vaccines manufactured with primary chicken embryo, rabbit kidney, or monkey kidney cell cultures are contaminated with BVDV RNA (17,43). As BVDV RNA or infectious BVDV in FBS is the most likely source of the contamination of human biologicals, FBS control is certainly important (10).…”

Section: Discussionmentioning

confidence: 88%

Stable High-Producer Cell Clone Expressing Virus-Like Particles of the Japanese Encephalitis Virus E Protein for a Second-Generation Subunit Vaccine

Kojima

Yasuda

Asanuma

et al. 2003

J Virol

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We produced and characterized a cell clone (J12#26 cells) that stably expresses Japanese encephalitis virus (JEV) cDNA, J12, which encodes the viral signal peptide, premembrane (prM), and envelope (E) proteins (amino acid positions 105 to 794). Rabbit kidney-derived RK13 cells were transfected with a J12 expression plasmid, selected by resistance to marker antibiotics, and cloned by two cycles of a limiting-dilution method in the presence of antibiotics, a procedure that prevents the successful generation of E-producing cell clones. J12#26 cells secreted virus-like particles containing the authentic E antigen (E-VLP) into the culture medium in a huge enzyme-linked immunosorbent assay-equivalent amount (2.5 g per 10 4 cells) to the internationally licensed JE vaccine JE-VAX. E-VLP production was stable after multiple cell passages and persisted over 1 year with 100% expressing cells without detectable cell fusion, apoptosis, or cell death, but was suspended when the cells grew to 100% confluency and contact inhibition occurred. Mice immunized with the purified J12#26 E-antigen without adjuvant developed high titers of neutralizing antibodies for at least 7 months and 100% protection against intraperitoneal challenge with 5 ؋ 10 6 PFU of JEV when examined according to the JE vaccine standardization protocol. These results suggest that the recombinant E-VLP antigen produced by the J12#26 cell clone is an effective, safe, and low-cost second-generation subunit JE vaccine.Japanese encephalitis virus (JEV), a member of the flavivirus family, is the causative agent of Japanese encephalitis (JE), which is a pandemic infectious disease of major public health importance in Asia (9, 48). Vaccination is the only effective way to prevent flavivirus infection in humans and domestic animals. Inactivated JEV and tick-borne encephalitis virus vaccines and attenuated yellow fever virus vaccine are in widespread production and use, whereas other flavivirus vaccines are under development or in human trials (6,26,37). The only licensed JE vaccine, JE-VAX, which is distributed commercially and available internationally, is formalin-inactivated JEV prepared from a number of JEV-infected mouse brains. The brain-derived whole virion vaccine is costly to manufacture and carries potential risks of allergic reactions to brain basic proteins or contamination by mouse prion proteins, and there are biosafety issues of manufacturing an infectious pathogen. Thus, the development of second-generation JE vaccines that are not derived from the brain, do not involve infectious JEV, and are of low cost is a top priority.The 53-kDa envelope (E) glycoprotein of JEV has an important role in virus adhesion and entry into target cells through receptor binding (20,34) and, therefore, in inducing neutralizing antibodies that protect hosts against JEV infection (8,24,32,36). The protective epitopes on the E antigen are suggested to be formed in highly conformational structures of JEV virions (20, 34) based on antigenic analyses with panels of monoclonal ant...

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Section: Discussionmentioning

confidence: 88%

Stable High-Producer Cell Clone Expressing Virus-Like Particles of the Japanese Encephalitis Virus E Protein for a Second-Generation Subunit Vaccine

Kojima

Yasuda

Asanuma

et al. 2003

J Virol

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“…In the second experiment, the positive rate was 12 (27.9%) out of 43 lots of human live virus vaccines produced by six Japanese manufactures [40]. An examination on interferon for human use showed a percentage of 30.4% out of 46 tested samples [23].…”

Section: Discussionmentioning

confidence: 92%

“…During an experimental study in Japan, pestiviral RNA was also detected in live virus vaccines for human use [24,40]. The vaccines were produced by different pharmaceutical companies, regularly authorized and commercialized: two monovalents against mumps and rubella and two polyvalents against measles, mumps and rubella.…”

Section: Bovine Viral Diarrhea Virus 1 (Bvdv-1) Bovine Viral Diarrhementioning

confidence: 99%

Genotypes of Pestivirus RNA Detected in Live Virus Vaccines for Human Use.

Giangaspero

Vacirca

Harasawa

et al. 2001

The Journal of Veterinary Medical Science

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ABSTRACT. Live virus vaccines for human use, 29 monovalent vaccines against measles, mumps, rubella or polio, eight polyvalent vaccines against measles-mumps-rubella and one bacterial polyvalent vaccine against Streptococcus pneumoniae, were tested by reverse transcriptase-nested PCR for the presence of petivirus or pestivirus RNA. Twenty-four samples were selected from European manufacturers, ten were from U.S.A. and four from Japan. Five (13.1%) out of 38 tested samples were positive for pestivirus RNA. Three vaccines (rubella and two measles) were from Europe and two (mumps and rubella) from Japan. The 5'-untranslated genomic region of the contaminant pestivirus RNA were amplified by reverse transcription-PCR and sequenced. Analyses based on primary nucleotide sequence homology and on secondary structures, characteristic to genotypes, revealed that the cDNA sequences belonged to bovine viral diarrhea virus (BVDV). A cDNA sequence, detected from one measles sample, belonged to BVDV-1b genotype. Pestiviral cDNA detected from the Japanese mumps and rubella vaccine samples, belonged to the BVDV genotypes 1a and 1c, respectively. Analysis on two cDNA sequences detected from measles and rubella vaccine samples from Europe showed their appurtenance to a new genotype, BVDV-1d. These findings indicate that contamination by animal pestivirus may occur in biological products for human use.

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“…Also BVDV-2 was reported as a contaminant of vaccines for veterinary use, and responsible of an outbreak of BVDV in Dutch cattle farms subsequent to the use of contaminated vaccines [26]. The BVDV-1 contamination of live virus vaccines for human use was also reported to occur in Japan [27,28], USA [29] and Europe [30]. During an experimental study in Japan, pestiviral RNA was also detected in live virus vaccines for human use [27,28].…”

mentioning

confidence: 99%

“…The BVDV-1 contamination of live virus vaccines for human use was also reported to occur in Japan [27,28], USA [29] and Europe [30]. During an experimental study in Japan, pestiviral RNA was also detected in live virus vaccines for human use [27,28]. The vaccines were produced by different pharmaceutical companies, regularly authorized and commercialized: two monovalents against mumps and rubella and two polyvalents against measles, mumps and rubella.…”

mentioning

confidence: 99%

Pestivirus Species Potential Adventitious Contaminants of Biological Products

Giangaspero¹

2013

Trop Med Surg

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Application of PCR for Detection of Mycoplasma DNA and Pestivirus RNA in Human Live Viral Vaccines

Cited by 13 publications

References 0 publications

Stable High-Producer Cell Clone Expressing Virus-Like Particles of the Japanese Encephalitis Virus E Protein for a Second-Generation Subunit Vaccine

Stable High-Producer Cell Clone Expressing Virus-Like Particles of the Japanese Encephalitis Virus E Protein for a Second-Generation Subunit Vaccine

Genotypes of Pestivirus RNA Detected in Live Virus Vaccines for Human Use.

Pestivirus Species Potential Adventitious Contaminants of Biological Products

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