Published Date: 2016-09-22 15:53:09
Subject: PRO/AH/EDR> Bluetongue virus - Israel: Tainted imported sheep-pox vaccine, untyped, RFI
Archive Number: 20160922.4508256
BLUETONGUE VIRUS - ISRAEL: TAINTED IMPORTED SHEEP-POX VACCINE, UNTYPED, REQUEST FOR INFORMATION
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Date: Thu 22 Sep 2016 [accessed]
Source: Vaccine 34 (2016) [edited]
Citation: V. Bumbarov, N. Golender, O. Erster and Y. Khinich. Detection and isolation of Bluetongue virus from commercial vaccine. Vaccine. 2016; 34: 3317-23., abstract available at: http://www.ncbi.nlm.nih.gov/pubmed/?term=27171751, [subscription required for full paper]
In this report we describe the detection and identification of Bluetongue virus (BTV) contaminations in commercial vaccines. BTV RNA was detected in vaccine batches of Lumpy skin disease (LSD) and Sheep pox (SP) using quantitative PCR (qPCR) for VP1 and NS3 genes. Both batches were positive for VP1 and NS3 in qPCR. The LSD vaccine-derived sample was positive for VP1 and VP2 in conventional PCR. The SP vaccine-derived sample was examined by amplification of VP1, VP4, VP6, VP7, NS2 and NS3 gene segments in conventional PCR. The SP vaccine-derived sample was further propagated in embryonated chicken eggs (ECE) and Vero cells. Preliminary sequence analysis showed that the LSD vaccine-derived sequence was 98-99 percent similar to BTV9. Analysis of the 6 genomic segments from the SP vaccine-derived isolate showed the highest similarity to BTV26 (66.3-97.8 percent). These findings are particularly important due to the effect of BTV on cattle and sheep, for which the vaccines are intended. They also demonstrate the necessity of rigorous vaccine inspection and strict vaccine production control.
[The following excerpt (references excluded) from the discussion chapter of the above paper illuminates the significance and potential implications of the reported findings:
"Detection of infective viral contamination was previously reported in human vaccines. However, the potential danger in the case reported here is significantly different from the discovery of avian retrovirus or porcine viruses in human vaccines, as these were found to be non-hazardous to humans, while the discovery of BTV in a vaccine intended for use in sheep or cattle, may result in a clinical infection.
"Nucleotide sequence analysis indicated that the LSDV-originated sequence is closely related to BTV serotype 9. The weak signal obtained from the LSDV vaccine, the negative NS3 amplification, and the unsuccessful culturing of the virus, may indicate that the contamination resulted from a very small amount of the virus, or from inactivated viral material, with putative low risk of infection. Contrariwise, the successful BTV culturing from the Sheep pox vaccine batch demonstrated that it may well be infectious, if administrated during vaccination. This may result in spreading of the virus among a previously free, susceptible population, through a vaccination campaign. Moreover, preliminary sequence analysis of the contaminated material showed that the SP-derived isolate was clearly different from other annotated serotypes. Nucleotide sequence analysis of 6 genomic segments indicated that it is close, but not identical, to BTV serotype 26 (66.3-97.8 percent similarity), and it is different from serotypes previously identified in Israel and Europe.
"The introduction of potentially pathogenic BTV serotype to a previously free herd or flock, may lead to an outbreak with severe consequences. It should be noted, though, that only one report was published, of a BTV-contaminated canine vaccine and no BTV outbreaks were reported as a result of vaccine contamination, to the best of our knowledge. Furthermore, introduction of a new serotype from a genetically dynamic pathogen such as BTV could be harmful even if the introduced serotype by itself has low virulence. Since reassortment and recombination events are common among BTV serotypes, they can readily generate new serotypes with new properties".
Contamination of live animal vaccines with pathogenic viruses is a well known, serious hazard requiring the full attention of those (in-plant and external/official) bodies responsible to assure the safety of biologicals. Each master seed must be tested to ensure its identity and shown to be free from adventitious viruses. A spectacular, early incident of vaccine contamination occurred in the 1930s following the use of formalin-inactivated sheep brain as a source for 'louping ill' vaccine, which led to the transmission of scrapie to over 1000 Scottish sheep from one vaccine lot. Later, sheep vaccines have been found contaminated on several occasions, particularly by pestiviruses (eg border-disease virus). An event of sheep-pox vaccine contaminated by the Aujeszky virus was reported in Kyrgyzstan and Uzbekistan (20131023.2016988). Other viruses may be involved as well, for example when the same plant produces different viral vaccines at the same time while biosecurity is less than optimal.
The viable BT virus found by the Israeli researchers to contaminate the imported commercial sheep-pox vaccine, addressed in the current paper, was identified as close, but not identical, to BTV serotype 26. The final identity of this contaminant, which could have been inoculated into sheep wherever this batch may have been injected to sheep, is of interest for reasons laid-out in the above discussion - and is hereby requested, in case determined. - Mod.AS
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