Update on the current status of rotavirus vaccines- Rotarix® and RotaTeq®

The Health Sciences Authority (HSA) has on 23 March 2010, informed healthcare professionals on the findings of DNA fragments of porcine circovirus 1 (PCV-1) in the rotavirus vaccine, Rotarix®, by an independent research team from the University of California, San Francisco. Additional studies have since been performed by the companies manufacturing rotavirus vaccines to further assess the presence and findings of PCV DNA fragments in these vaccines. HSA would like to update healthcare professionals on the current findings from these studies as well as the interim local recommendations on the use of rotavirus vaccines until a decision is made following HSA's review of this matter.

Rotarix® (GlaxoSmithKline, GSK) and RotaTeq® (Merck Sharp and Dohme, MSD) are the two rotavirus vaccines licensed in Singapore since October 2005 and July 2007 respectively for the vaccination of infants 6 weeks and older against gastroenteritis due to rotavirus infection. Both vaccines have been studied extensively in clinical trials involving tens of thousands of patients and used in millions of patients globally in clinical practice. There have been no significant safety issues observed with these vaccines to date.

Summary of the Update on Rotavirus Vaccines Provided on 23 March 2010

Using a powerful new method, an independent research team from the University of California, San Francisco (UCSF) had identified DNA fragments of PCV-1 in the rotavirus vaccine, Rotarix®. Further investigations conducted by GSK and the US FDA confirmed the presence of PCV-1 DNA fragments in the human rotavirus vaccine and its starting materials. As the significance of the PCV-1 DNA fragments was still not completely known, HSA had advised healthcare professionals to consider the options of temporarily deferring immunisation with Rotarix® or use an alternative vaccine until more information was available. RotaTeq® was not found to contain the PCV-1 DNA fragments at that point in time.

New information on Rotarix® and RotaTeq®

With regard to Rotarix® vaccine, preliminary evidence from ongoing investigations show that the PCV-1 DNA fragments in the final vaccine product is unlikely to cause infection in human cell lines. Current available data also suggests that there were no cases of PCV-1 infection in infants who had received Rotarix® in clinical trials. Infectivity assays are still in progress to expand the observation period and number of tested cell lines.

While initial tests for PCV1 by the researchers at UCSF and US Food and Drugs Administration (FDA) did not show the presence of PCV DNA fragments in RotaTeq®, additional testing conducted by MSD detected the presence of PCV1 and porcine circovirus 2 (PCV-2) fragments in vaccine intermediates and PCV DNA in the final vaccine. The number of copies of these fragments in the RotaTeq® intermediates and final product lots appear to be several log-folds less than those detected in the Rotarix® intermediates and final product lots. The significance of this new finding is still not completely known and additional tests are currently in progress.

More information on PCV-1 and PCV-2

PCV-1 and PCV-2 DNA are not derived from the pig mammal. PCV-1 is found in pigs but it has not been linked to any animal disease. PCV-1 does not multiply in humans and is not known to cause illness in humans.

PCV-2 is a variant of PCV-1 and has been known to cause illness in pigs. There is however no documentation so far that PCV-2 can infect humans and is not known to cause illness in humans.

Outcome of the US FDA Vaccines and Related Biological Products Advisory Committee Meeting

The US FDA convened a Vaccines and Related Biological Products Advisory Committee meeting on 7 May 2010 to discuss the above findings. The advisory panel was generally of the opinion that the two rotavirus vaccines, RotaTeq® and Rotarix®, should continue to be used as the benefits of vaccination outweigh the risks of contamination with PCV DNA fragments. The committee noted that the benefit of rotavirus vaccination in terms of reducing gasteroenteritis-related fatalities and hospitalisations in the United States outweighed the risk of PCV infectivity. From the data presented at the meeting, it was shared that there were no signs so far of illness in people caused by PCV.

The FDA will be coming up with a decision on the use of rotavirus vaccine following the advisory committee's meeting in the near future. In the meantime, there are no changes to the temporary deferment of Rotarix® use and RotaTeq® continues to be allowed for use in the US.

HSA's interim recommendations

HSA will be convening a meeting with the Ministry of Health (MOH) and its Expert Committee of Immunisation (ECI) in the next few days to discuss the impact of the above information on the use of the 2 licensed rotavirus vaccines in Singapore.

In the interim, healthcare professionals may wish to consider the options of deferring the use of Rotarix® or using Rotateq® based on an assessment of the individual patient until further advice is provided. It is to be noted that rotavirus vaccination is an optional vaccination that is not included in the local Childhood Immunisation Programme.