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Posted by on May 7, 2010 in Infectious diseases, Pharma

Now Rotateq Has PCV DNA Fragments; Trypsin May Be Source

Now Rotateq Has PCV DNA Fragments; Trypsin May Be Source

Trypsin_PAA.jpg

A recent, independent search for viral DNA in certain vaccines* revealed nucleic acids of a common pig virus (PCV1) in GSK’s Rotarix but not in Merck’s Rotateq. The results of the California-based study, which were published online last month in the Journal of Virology, led the FDA to suspend the use of Rotarix in Marchdespite the fact that 1) the DNA fragments were present from the vaccine’s inception** and 2) PCV1, a ubiquitous virus, is not known to cause disease in humans or pigs. (For more background on this story, start here.)

Now the FDA is reporting that Merck’s vaccine contains DNA fragments of PCV1 and PCV2. Merck evidently detected the nucleic acids in its product with a more sensitive assay, reports the WSJ. PCV2, like PCV1, does not cause human disease; however, it may sicken pigs. Merck and the FDA speculate that the source of the DNA fragments may be trypsin, a protease which is used in the cell-culture growth of the attenuated vaccine virus.

Commercial trypsin may be obtained from bovine or porcine pancreas. According to one commercial pamphlet, the enzyme can be contaminated with porcine viruses, especially porcine parvovirus (which is not known to cause human disease). There is evidently some give and take when using methods (eg, chemical or filtering) to inactivate or remove contaminating viruses during trypsin manufacture. Gamma irradiation and heat inactivation, while “officially recognized,” are “aggressive” and affect trypsin yield, says PAA. Short wave-length UV light is advocated by the company to destroy viral nucleic acids, without compromising the biologic activity of trypsin.

According to the FDA by way of the WSJ, both Rotarix and Rotateq have been given to millions of babies to reduce the risk of gastrointestinal disease due to rotavirus. However, given that trypsin may be the source of the PCV DNA fragments and is used widely in the biotech industry, contamination may extend well beyond mere vaccine production.

My speculation: Vast potential for the contamination of products with viral nucleic acids with negligible or no risk of illness.

Today’s FDA meeting, which was already scheduled to discuss the potential safety issues of PCV1 DNA in Rotarix, will also address the newly found DNA fragments in Rotateq.

* Live, attenuated.

** Meaning that the safety of the contaminated Rotarix vaccine was assessed in approval-required clinical studies.

Image of commercial trypsin from PAA.

05/08/10 update: Yesterday an FDA advisory panel recommended the continued use of Rotarix and Rotateq, according to the WSJ and other news sources. It should be stressed that, while some coverage (I’m talking about you, MedPage Today) indicates that the actual viruses PCV1 or PCV2 are present in the vaccines, only DNA fragments of the viruses have been detected. This fact substantially reduces, if not eliminates, any infectious possibility. Moreover, neither virus is known to cause human disease.

05/15/10 update: Yesterday the FDA sanctioned the continued use of both the Rotarix and Rotateq vaccines. The decision was “[b]ased on a careful review of a variety of scientific information.” In hindsight, FDA officialsin a pervasive, overly cautious frame of mindjumped the gun when it first suspended the use of Rotarix in March.

bmartin (1130 Posts)

A native East Tennessean, Barbara Martin is a formerly practicing, board-certified neurologist who received her BS (psychology, summa cum laude) and MD from Duke University before completing her postgraduate training (internship, residency, fellowship) at the Hospital of the University of Pennsylvania in Philadelphia. She has worked in academia, private practice, medical publishing, drug market research, and continuing medical education (CME). For the last 3 years, she has worked in a freelance capacity as a medical writer, analyst, and consultant. Follow Dr. Barbara Martin on and Twitter.