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

Abstract

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.

Genetic Variety of Bovine viral diarrhea virus 2 Strains Isolated from Sheep

“…The results of the PNS method are essentially qualitative and provide the exact species classification of an isolate, although they offer no percentage values for homology among species and genotypes. According to the PNS method, the BVDV-1 species have been segregated into fourteen genotypes [10,15,16]. The taxonomic status of a giraffe strain was characterized, based on the 5'-UTR, as a new cluster among Pestivirus species [12].…”

Detection of Inhibition of Bovine Viral Diarrhea Virus by Aromatic Cationic Molecules

“…Noncytopathic biotypes of BVDV have been identified in commercially available lots of fetal bovine serum despite testing by the manufacturer (6,45). Consequently, BVDV has been identified in commercially available bovine, canine, feline, and primate cell lines (16,19), human viral vaccines for measles-mumps-rubella (18,21), and interferons for human use (20). Viral contamination of biologicals for human use may be the reason BVDV-specific antibodies have been found in some samples of human serum (17).…”

Pestivirus Species Potential Adventitious Contaminants of Biological Products

“…Similarly, interferon for human use was found contaminated by BVDV-1 RNA [31]. Further studies demonstrated the occurrence of Pestivirus contamination in live virus vaccine for human use also in Europe [30]. The characterization, based on primary nucleotide sequence homology and secondary palindromic sequence structure in the 5'-UTR, revealed positive samples contaminated with the BVDV-1 genotype Ib.…”

“…Other particularly important aspects related to the potential of iatrogenic infections are the possible contamination of modified live vaccines and the capacity of pestiviruses to cross placental barrier and determine vertical transmission [30]. Therefore, a definitive risk during pregnancy has to be taken into account.…”

“…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].…”