Vaccines put the runs on the board

Late last year, the federal government added two new vaccines to the pharmaceutical benefits scheme (PBS).

These vaccines will protect infants against rotavirus infection, the most common cause of gastroenteritis worldwide. One or both of them will become part of the national immunisation program from July 2007, at a cost of $124.4 million over five years.

Rotavirus describes a family of RNA viruses characterised by their wheel-like appearance when viewed by electron microscopy (the name is derived from the Latin rota, meaning "wheel").

Australian scientist Professor Ruth Bishop discovered rotavirus in 1973 as a cause of childhood gastroenteritis, and is now in the unusual situation of seeing her hard work potentially help millions of kids.

Rotavirus is a global problem. An estimated 600,000 children worldwide die each year from diarrhoea caused by rotavirus gastroenteritis, and 80 per cent of these live in developing countries. This incidence equates to one child every minute.

In fact, almost every child in the world will suffer at least one infection by the time they are five years old, with the peak incidence of rotavirus-induced disease seen in children between six months and two years of age.

In Australia, rotavirus infection accounts for 10,000 hospitalisations each year. It is the largest single cause of admissions in children under five years old, and half of these cases are in kids under one.

Indigenous populations in Australia are particularly affected, with Aboriginal children three to five times more likely to be hospitalised from rotaviral-related diarrhoea by the age of five than the remainder of the Australian population.

Acknowledging this, and the 200 to 600 reported cases in the Northern Territory each year, the territory government introduced Australia's first vaccination program earlier this year, prior to the PBS listing.

At the 2007 annual scientific meeting of the ASM in Adelaide in July, Dr Carl Kirkwood from the Murdoch Childrens Research Institute (MCRI) in Melbourne will discuss the new vaccines and report on the state of current rotavirus strains and infections in Australian children.

Kirkwood heads the Enteric Virus Group at the MCRI, and his laboratory hosts the National Rotavirus Reference Centre. Together with nine collaborating laboratories, the centre undertakes surveillance and serotype characterisation of rotavirus strains causing severe gastroenteritis in Australian children.

Kirkwood's group is also the World Health Organisation Collaborating Laboratory for Child Health, and the Asian Rotavirus Surveillance Network reference and training laboratory.

At the ASM meeting, Kirkwood will discuss the epidemiological studies that form part of these surveillance duties, an important component of rotavirus vaccine evaluation and implementation programs.

"We know that five different rotavirus serotypes are responsible for 80 to 90 per cent of infection worldwide," Kirkwood says. "In Australia, serotype G1 is the most common type identified during the past decade, however, serotype G3 has emerged as the major cause of disease in the past few years. We also occasionally identify rare serotypes in Australia, including the G6, G8 and G12 strains."

The newly licensed vaccines are both live attenuated forms, but differ in composition and dosage requirements. RotaTeq (CSL/Merck) is a human-bovine reassortant vaccine containing five virus types, while Rotarix vaccine (GlaxoSmithKline) contains a single, attenuated human strain.

Kirkwood will discuss the large-scale and stringent clinical trials undertaken for both vaccines in many different countries prior to licensing.

The efficacy of RotaTeq and Rotarix are similar, at around 70 per cent against rotavirus gastroenteritis of any severity and 85-100 per cent against severe disease.

"This is despite being based on slightly different principles to achieve protection," Kirkwood says.

He will also highlight these differences and comment on their potential significance.

Licensing and PBS registration of the rotavirus vaccines was welcomed by paediatricians, general practitioners, child carers and any others who deal with the annual swathe of children suffering from rotavirus gastroenteritis.

In particular, it was happy news for Kirkwood and his colleagues, who include Ruth Bishop. Although now semi-retired, she retains an active interest in the group and in continuing efforts initiated by herself and long-time colleague, Professor Graeme Barnes, to develop their own vaccine against rotavirus infection.

Developing nations

While the MCRI team is happy that Australian babies and the community will benefit from the recent announcement, its ultimate goal is to see a rotavirus vaccine being distributed in developing nations.

"Neither of the two vaccines are really targeted for that market nor feasible due to cost," Kirkwood says.

The vaccine being developed by the MCRI group is based on a neonatal strain of the virus discovered by Bishop and Barnes in 1988. Infection with this strain does not cause disease, making it an excellent vaccine candidate.

It is being produced in conjunction with BioFarma PT, a manufacturer of pharmaceuticals in Indonesia, where the annual death toll from rotavirus infection is 10,000 children.

MCRI has also contracted Q-Gen in Queensland to run early-phase clinical trials in Indonesia and New Zealand initially (Australia is unsuitable now that children here will be vaccinated).

Converting the single rotavirus strain into a vaccine proved much more difficult than expected for the group, led at the time by Bishop and now by Kirkwood. Although AMRAD had an initial financial interest in the work, funding to complete the research has been patchy.

However, the project recently secured important seed funding from the WHO, followed by further financial support from BHP Billiton.

The biggest problem for the team recently was that most of the big money worldwide went into the two major efforts and to other US developments. Two other rotavirus vaccines are also being developed specifically for the poorer children of the world - one by an Indian/US effort and one at the National Institutes of Health in the US.

However, Kirkwood says this is actually a good thing for his group. "Several global efforts will be needed to get to all the kids at risk, and we will need multiple companies distributing the vaccine, from both a logistical and production standpoint."

The current focus of Kirkwood's group is twofold. It needs to get the vaccine produced in large amounts for clinical trials and Phase I/II trials have to be established.

Success in the current round of NHMRC funding will ensure a quicker realisation of these goals, and Kirkwood is quietly confident that the recent support from the WHO and major Australian industry sources will help in this endeavour.

The ASM conference is being held in Adelaide from July 9 to 13. See www.asm2007.org for more.