Conceiving the cervical cancer vaccine

A 'cure' for cancer may be the dream endpoint for many a medical narrative, but the reality of the situation is that prevention is the more achievable aim to tackle this killer disease.

Healthier lifestyles and avoiding harmful substances such as tobacco are key to many campaigns to stem the growth of certain cancers, but one area where research has taken off in the past 20 years is the idea of a cancer 'vaccine'.

Having been around since the days of Edward Jenner's smallpox vaccine in the 18th century, vaccines have gone on to save millions of lives throughout the world, protecting from such conditions as polio, tuberculosis, measles and 'flu.

Cancer vaccines have come into medical science as a more recent development, however, with one of the most successful fights so far coming against cervical cancer.

The disease is the third most common cancer in women worldwide, causing 275,000 deaths a year, according to the World Health Organisation (WHO).

This is despite the introduction of Pap smear screenings bringing mortality rates down in developed countries by allowing earlier treatments. However, cervical cancer is still the second highest cause of cancer death in women in developing nations.

In March 1991 one of the first steps was taken towards finding a way to prevent the cancer in the first place, when researchers Professor Ian Frazer, Dr Jian Zhou and Dr Xiao-Yi Sun discovered something that made the development of a vaccine possible.

Although not necessarily working directly against the cancer itself, cervical cancer vaccines protect against the human papilloma virus (HPV), which is thought to cause most cases of cervical cancer.

The breakthrough of Prof Frazer and his team, who were working at the University of Queensland in Australia, was to combine two proteins into a virus-like particle (VLP) that resembled the HPV shell of the real HPV particle.

With this, they knew it would be possible to create a vaccine for HPV, with the VLP's ability to elicit strong T cell and B cell immune responses that would protect against the development of the real virus.

“The day we first saw the picture of these virus-like particles we knew that if anything was going to be a vaccine, that would be,” Frazer said later in an interview with the Australian Broadcasting Corporation.

Scotland-born Frazer and Chinese virologist Zhou met at Cambridge University in England in 1989, bonding during evenings spent researching while their colleagues were “down at the pub”, according to an interview with Frazer by the Australian Academy of Science.

The meeting of minds brought together Frazer's immunology background and Zhou's expertise in molecular biology, with the pair's research seeing gene cloning and expression replacing the traditional vaccine approach of growing a virus then killing it or making it safe.

This collaboration continued in Brisbane, Australia, where Frazer had been based before his Cambridge sabbatical, with Frazer helping to arrange Zhou's visa on the way – a document that was not easy to gain for a Chinese national at the time.

Following the discovery of the VLP, Frazer and Zhou published a paper in the journal Virology and filed a provisional application for a patent in June 1991.

Soon, pharma companies became involved in the research, with partial patents sold to both Australian biopharma CSL Ltd and Merck & Co, to develop a vaccine, and subsequently to GlaxoSmithKline (GSK).

Through this funding, trials investigating the efficacy of the vaccines began, progressing to the first human trial in 1998, before Merck finally gained approval for HPV vaccine Gardasil in Australia and the US in 2006.

The approval followed studies that had shown an almost 100 per cent success rate against HPV-16 and HPV-18 – the two strains of HPV that cause 70 per cent of HPV-related cervical cancer cases.

A year later, GSK gained its first approval for Cervarix, which was also based on the original work of Frazer and Zhou 16 years before.

Unfortunately, Zhou did not live to see the real benefits of his work, dying unexpectedly in 1999, leaving behind a wife, a son and  the legacy of a leap forward in the battle against cancer.

For his part, Frazer has received numerous accolades and awards across the scientific and medical world, including the Howard Florey Medal for Medical Research, the Australian Medical Association Gold Medal and Australian of the Year in 2006.

However, Frazer is always keen to make sure that each honour means more than simply rewarding one individual.

Speaking to the Australian Academy of Science, he said: “It's nice to get the recognition for science. I think it's very important to show the community at large that science contributes to society.”

The Author
Tom Meek, web editor at PMLiVE