This report describes FDA's laboratory response to the 2010 reports that porcine circovirus type 1 (PCV-1) DNA was present in U.S.-licensed rotavirus vaccines and in cells used to produce inactivated poliovirus vaccines. In the present study, Rotarix® (GlaxoSmithKline, Rixenxart, Belgium) was found to contain full-length PCV-1 genomes that are particle-associated, and cell culture assays in swine testis (ST) and PCV-free porcine kidney (PK-15) cells confirmed that PCV-1 sequences in this vaccine represent infectious virus. RotaTeq® (Merck and Co., West Point, PA, USA) contained small PCV-1 and PCV-2 genome fragments, but did not contain detectable larger portions of (or full-length) PCV genomes, and cell culture assays did not amplify PCV from this vaccine. Inactivated poliovirus vaccine bulks (GlaxoSmithKline) were also negative for the presence of PCV by cell culture infectivity assay. In these vaccines, molecular characterization of PCV nucleic acids was useful for predicting the results of cell culture assays.
"On May 14, 2010, the FDA issued a recommendation for pediatricians to resume use of Rotarix and to continue use of RotaTeq . Subsequent testing by the vaccine manufacturers identified that the PCV material was introduced into both rotavirus vaccines through porcine-derived trypsin, a reagent used in the cell-culture growth process of vaccine production, commencing very early in the development process  . The use of cells or biological products from other species in the production of vaccines can lead to leakage of cellular DNA and the introduction of noninfectious proviral DNA . "
[Show abstract][Hide abstract] ABSTRACT: In 2010, researchers reported that the two US-licensed rotavirus vaccines contained DNA or DNA fragments from porcine circovirus (PCV). Although PCV, a common virus among pigs, is not thought to cause illness in humans, these findings raised several safety concerns. In this study, we sought to determine whether viruses, including PCV, could be detected in ileal tissue samples of children vaccinated with one of the two rotavirus vaccines. A broad spectrum, novel DNA detection technology, the Lawrence Livermore Microbial Detection Array (LLMDA), was utilized, and confirmation of viral pathogens using the polymerase chain reaction (PCR) was conducted. The LLMDA technology was recently used to identify PCV from one rotavirus vaccine. Ileal tissue samples were analyzed from 21 subjects, aged 15-62 months. PCV was not detected in any ileal tissue samples by the LLMDA or PCR. LLMDA identified a human rotavirus A from one of the vaccinated subjects, which is likely due to a recent infection from a wild type rotavirus. LLMDA also identified human parechovirus, a common gastroenteritis viral infection, from two subjects. Additionally, LLMDA detected common gastrointestinal bacterial organisms from the Enterobacteriaceae, Bacteroidaceae, and Streptococcaceae families from several subjects. This study provides a survey of viral and bacterial pathogens from pediatric ileal samples, and may shed light on future studies to identify pathogen associations with pediatric vaccinations.
Advances in Virology 03/2014; 2014:720585. DOI:10.1155/2014/720585
"Using deep sequencing, Delwart and colleagues recently identified PCV-1 contamination in several batches of Rotarix, a childhood vaccine for Rotavirus . PCV-1 and PCV-2 contamination in Rotarix has been confirmed by other research groups [8e10] and in one study the vaccine associated PCV-1 was shown to infect cultured porcine kidney cells . Serologic studies examining potential PCV infection in humans have yielded conflicting results. "
[Show abstract][Hide abstract] ABSTRACT: There are two porcine circovirus (PCV) genotypes, PCV-1 and PCV-2. In pigs, PCV-1 infection is asymptomatic but PCV-2 infection can cause severe respiratory disease and other pathology. Although humans ingest PCV-contaminated foods and are exposed to PCV through other sources, the potential of PCV-2 as a zoonotic agent in humans and other species has not been fully explored. Here, four recombinant proteins derived from the PCV-2 capsid gene were examined as antigens using the Luciferase Immunoprecipitation System (LIPS) assay for serological analysis of PCV-2 infection. PCV-2-CAP-Δ1 was the optimum recombinant protein in the LIPS assay with a sensitivity of 93% and specificity of 100% using porcine samples. Testing of healthy human blood donors, equine and bovine serum samples failed to demonstrate the presence of anti-PCV-2 antibodies. Additionally, analysis of two high-risk human groups, cystic fibrosis patients taking porcine derived oral supplements and type I diabetes patients who had undergone porcine islet cell transplantation, showed no evidence of anti-PCV-2 antibodies. These results extend the extensively demonstrated use of LIPS as a robust approach for identifying humoral responses and provide evidence that PCV-2 is likely not infectious in humans.
"It was estimated that over 10 5 or 10 6 PCV1 DNA molecules may be present in each dose of the contaminated vaccine [6e8]. Later, DNA from PCV1 and porcine circovirus type 2 (PCV2) was detected in a rotavirus vaccine from another manufacturer (B)  . PCV1 and 2 are small icosahedral, non-enveloped viruses that contain circular, single-stranded DNA molecules of 1759 bp (PCV1) or 1768 bp (PCV2) . "
[Show abstract][Hide abstract] ABSTRACT: DNA from porcine circovirus type 1 (PCV1) and 2 (PCV2) has recently been detected in two vaccines against rotaviral gastroenteritis from manufacturers A and B. We investigated if PCV1 sequences are present in other viral vaccines. We screened seeds, bulks and final vaccine preparations from ten manufacturers using qRT-PCR. We detected 3.8 × 10³ to 1.9 × 10⁷ PCV1 DNA copies/milliliter in live poliovirus seeds for inactivated polio vaccine (IPV) from manufacturer A, however, following inactivation and purification, the finished IPV was PCV1-negative. PCV1 DNA was not detectable in live polio preparations from other vaccine producers. There was no detectable PCV1 DNA in the measles, mumps, rubella and influenza vaccines analysed including material supplied by manufacturer A. We confirmed that the PCV1 genome in the rotavirus vaccine from manufacturer A is near full-length. It contains two mutations in the PCV cap gene, which may result from viral adaptation to Vero cells. Bulks of this vaccine contained 9.8 × 10¹⁰ to 1.8 × 10¹¹ PCV1 DNA copies/millilitre and between 4.1 × 10⁷ and 5.5 × 10⁸ DNA copies were in the final doses. We found traces of PCV1 and PCV2 DNA in the rotavirus vaccine from manufacturer B. This highlights the issue of vaccine contamination and may impact on vaccine quality control.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.