Rotavirus diarrhea vaccine Rotarix by GSK may contain pig virus, warns US FDA

Rotarix, a vaccine to fight rotavirus infection in children marketed by GlaxoSmithKline, may contain a pig virus, warned the U.S. Food and Drug Administration.

Rotarix is a vaccine indicated for the prevention of rotavirus gastroenteritis caused by G1 and non-G1 types (G3, G4, and G9). Rotarix is approved for use in infants 6 weeks to 24 weeks of age.

GSK has discovered trace amounts of the virus called PCV-1 in the vaccine Rotarix while working on the development of a new virus-discovery method.

An independent U.S. academic research team, using a novel technique, had earlier found DNA from porcine circovirus 1 (PCV1) in Rotarix, which is manufactured by GlaxoSmithKline.

Follow-up tests by GlaxoSmithKline and FDA scientists confirmed the academic team’s findings and confirmed that viral components have been present since the early stages of the vaccine’s development, including during clinical studies.

Preliminary testing by both the academic researchers and US FDA scientists of another licensed vaccine against rotavirus infection, RotaTeq, has not detected components of PCV1.

PCV-1 does not multiply in humans and is not known to cause rotavirus related illness in people, GSK said.

US FDA, however, has advised doctors to temporarily avoid using GlaxoSmithKline’s Rotarix vaccine for rotavirus after the drug maker found traces of a pig virus in the vaccine.

“There is no evidence at this time that there is a safety concern.  FDA is recommending that clinicians temporarily suspend use of Rotarix until we can learn more about the situation.  We will keep the public and the clinical community updated on our findings,” stated Dr. Margaret A. Hamburg, Commissioner for Food and Drugs.

Rotarix and RotaTeq are given by mouth to young infants to prevent rotavirus disease, which can cause severe diarrhea and dehydration and is estimated to be responsible for the deaths of more than 500,000 infants around the world each year, primarily in low- and middle-income countries.

Before the introduction of a rotavirus vaccine, rotavirus resulted in more than 50,000 hospitalizations and several dozen deaths in the United States each year, a US FDA release said.

US FDA licensed RotaTeq in 2006 and Rotarix in 2008.  Most children vaccinated in the United States received RotaTeq.

More than 69 million doses of Rotarix have been administered worldwide with no reports of illness caused by PCV-1, GlaxoSmithKline and the FDA said. Many meat products that contain PCV-1 are eaten by people regularly with no adverse effects.

Circoviruses have not been associated with illnesses in humans, and FDA has not required the routine testing of vaccines for these viruses.

Current US FDA guidance, released in March 2010, recommends that manufacturers consider testing for these agents.  FDA introduced this recommendation as an additional precaution for vaccines manufactured with animal-based components.

What is rotavirus?

Rotavirus is named after its characteristic wheel-like appearance when viewed under an electron microscope.  The viral genome is composed of 11 segments of double-stranded RNA that code for six structural and five nonstructural proteins.  It can be diagnosed through commercially available tests that detect the virus in stool.

Rotavirus infects the intestines.  The disease usually starts with fever, an upset stomach, and vomiting, followed by diarrhea.  The disease generally lasts 3-8 days.  In the United States, rotavirus infection generally occurs during the winter and spring.

There is no specific treatment for the rotavirus infection.  The most serious problem caused by the disease is dehydration, so symptoms are treated by rehydration.  Severe cases require administration of intravenous fluids in a hospital.

Rotavirus disease can be prevented with vaccination.

Rotavirus is usually spread when children touch or place in their mouths small, usually invisible amounts of fecal matter found on surfaces such as toys, books and clothing, or on the hands of caregivers.  The virus can also be transmitted through contaminated water or food, and possibly by respiratory droplets in a sneeze, cough, or exhalation.  The virus is very contagious.

arly all children are infected with rotavirus at some point before the age of 5.

Still, the FDA opted to issue its temporary warning about Rotarix due to GSK not being sure how the virus got into the vaccine and because Merck supplies a competing vaccine for rotavirus, which causes severe diarrhea in small children and is a leading cause of death in developing countries.

Rotavirus is the single most important cause of diarrhoea, responsible for 20 to 25% of all deaths due to diarrhoea and 6% of all deaths of children less than 5 years old.

Effective medical care results in only 20 to 40 children dying each year due to Rotavirus in the US, whilst in Africa the figures are between ten and fifteen thousand in children under 5.

In Africa and Asia alone, a Rotavirus with sixty per cent efficacy has the potential to save more than 1.5 million lives between 2010 and 2025.

Rotavirus kills over half a million children each year, the vast majority in the developing world, and whilst vaccines have already been licensed for use in many Western countries, they are not yet available in parts of Africa where they are needed most.

Now with WHO recommendation of rotavirus vaccine for global use vaccine makers see a huge demand several hundred million doses of rotavirus vaccine by all countries in the world in the coming years.

India alone will require 100 million vaccines, at three doses per child, it is estimated.

Among the Indian players, Bharat Biotech’s rotavirus vaccine 116E has entered phase 3 human studies in March this year.

Bharat Biotech and its funding partners have already invested $28-30 million in vaccine development so far. The Hyderabad-based Bharat Biotech is planning to spend another $30 million on phase three clinical trials alone.

The phase three trails will be mainly in India and will enroll 6,800 healthy infants Bharat Biotech expects to launch the rotavirus vaccine by 2011 in India.

Shantha Biotechnics is currently developing a multivalent vaccine against rotavirus in collaboration with the global nonprofit health organization PATH. PATH is an international, nonprofit organization enabling communities worldwide to break longstanding cycles of poor health

Shantha was expected to carry out the clinical trials following completion of preclinical toxicology studies in the year 2008.

Serum Institute of Pune and Biological Evans of Hyderabad are the other Indian companies having the rotavirus vaccine technology.

GlaxoSmithKline’s (GSK) launched Rotarix in India in 2008. Merck too plans to launch its vaccine, RotaTeq in India soon. Both versions for the vaccines are oral vaccines. GSK has priced its vaccine at Rs 1,000 per dose.