BioEd Online

After some 30 years of research, scientists have finally shown in clinical trials that vaccines can safely combat rotavirus, the leading cause of death from severe diarrhoea and dehydration in children.

One of the vaccines to pass muster in these trials has already been licensed for use in a few countries on the back of other, smaller tests. But experts say the unqualified success of two drugs in these larger trials, without negative side effects, is a major step towards getting them put into wider use.

This could have a huge impact on children's health. In developing countries, where dehydration can be tough to treat, it kills some half a million children each year. In the United States, rotavirus causes about 55,000 hospital admissions annually, and a few dozen deaths.

The two different vaccines in the trials were shown to drastically reduce the occurence of severe symptoms, by between 85 and 100%. The results are reported in the New England Journal of Medicine¹,².

Researchers hope that the vaccines, which are swallowed rather than injected, will become a routine part of the immunization repertoire given to babies alongside diphtheria and tetanus. "These results are really promising and very exciting," says Umesh Parashar, an infectious-disease specialist at the US Centers for Disease Control and Prevention in Atlanta, Georgia.

But the researchers caution that several obstacles remain before the therapies can start saving large numbers of lives in the developing world.

Trial and error

Scientists have been seeking a vaccine against rotavirus since the discovery of the pathogen in 1973. The virus, which has many different strains, infects almost every child in the world before they reach five years of age, although often with only mild effects. There is no drug treatment yet.

Investigators had some success with a vaccine called RotaShield in the late 1990s, but it was withdrawn after only nine months because it was found to trigger a rare but potentially fatal intestinal blockage in a handful of children. Though the vaccine would have undoubtedly saved many lives in the developing world, it proved untenable to offer a vaccine overseas that had been deemed too risky for the United States.

Researchers could not work out why the monkey rotavirus in the vaccine caused this problem, and feared that all rotavirus vaccines might be similarly scuttled. To prove that the new vaccines are safe, the teams enrolled more than 60,000 infants for each trial, in order to detect complications that might develop in only a few tens or hundreds.

Both vaccines appeared to avoid side effects and protected children against multiple strains of rotavirus. One, called Rotarix and manufactured by drug giant GlaxoSmithKline, contains a crippled strain of live human rotavirus¹. The other, a Merck vaccine dubbed RotaTeq, is made up of five different disabled rotaviruses, each a combination of strains from humans and cows².

Merck's RotaTeq could be available in US paediatric clinics later this year. An expert committee last month advised the US Food and Drug Administration (FDA) to approve the vaccine for use, thanks in part to the trial data.

Roadblocks

But experts in the field say they face several challenges before the rotavirus vaccine can be widely used. In the United States and other developed countries, Parashar suggests that a reputation for side effects may prevent doctors and parents from adopting the vaccines. "The concerns about safety will remain for a while," he says.

Researchers add that they must perform additional clinical trials to test whether the immunizations are as effective on children that are malnourished and harbour other infections, as is often the case in developing countries. The vaccine may also prove too expensive for widespread use in such places.

Non-profit groups including the Global Alliance for Vaccines and Immunizations are pushing to make the vaccines available in the developing world, and are supporting local trials of these vaccines along with the pharmaceutical companies.

Paediatrician David Matson of Eastern Virginia Medical School in Norfolk, Virginia, lead researcher in the RotaTeq trial, adds that there is concern that the vaccine could become less effective over time. Like the influenza virus, rotavirus can swap genes to produce strains that might evade the immune response provoked by the vaccine. This means that the vaccine might have to be regularly tweaked to target the most common circulating strains.