On a 1989 sabbatical he met virologistJian Zhou, and the two considered the problem of developing a vaccine for HPV – a virus that cannot be cultured without living tissue.[12] Frazer convinced Zhou to join him, and in 1990 they began to use molecular biology to synthesize particles in vitro that could mimic the virus. In March 1991 Zhou's wife and fellow researcher, Xiao-Yi Sun,[8] assembled by Zhou's instructions[13] two proteins into a virus-like particle (VLP),[14] resembling the HPV shell, from which HPV vaccine would ultimately be made.[5] The vaccine completely protects unexposed women against four HPV strains responsible for 70% of cervical cancers,[15][16] which kill about 250,000 women annually.[17][18] Frazer and Zhou filed a provisional patent in June 1991 and began work on developing the vaccine within UQ. To finance clinical trials, Australian medical company CSL, and later Merck, were sold partial patents.[19] (CSL has the exclusive license to sell Gardasil in New Zealand and Australia, Merck the license elsewhere.)[20]GlaxoSmithKline independently used the same VLP-approach to develop Cervarix, under a later US patent, licensing Frazer's intellectual property in 2005.[21]
Later in 1991 the research was presented at a US scientific meeting, and Frazer became Director of the Centre for Immunology and Cancer Research at the University of Queensland (later renamed The Diamantina Institute for Cancer, Immunology and Metabolic Medicine, where he held a personal chair as director). After three years in design, Gardasil went into testing, and Frazer became a professor in the university's Department of Medicine. In 1998 Frazer completed the first human trials for Gardasil, and became an Australian citizen.[4][14]
Pioneer Patent for VLPs and the HPV vaccine
US. 7,476,389, titled "Papilloma Virus Vaccines", was granted to co-inventors Ian Frazer and Jian Zhou (posthumously) on 13 January 2009. Its U.S. application was filed on 19 January 1994, but claimed priority under a 20 July 1992 PCT filing to the date of an initial [AU] Australian patent application filed on 19 July 1991.
Celebrity
In 2006 results from the four-year Phase III trials led to Australian and US regulatory approval.[14] Frazer's studies showed 100% efficacious protective immunity in HPV naïve women, but could not directly test protective immunity (against HPV exposure) in adolescent girls. As a surrogate test, antibody titer levels in vaccinated 9 to 15-year-old girls was shown high enough to give them the same level of immunity as vaccinated women.[22] It has been suggested that one way to bring cheaper equivalent vaccines to market is to mandate a similar induced immune response.[23]
In the 2007 resolution of their US patent lawsuit, Frazer's and Jian Zhou's heirs (Zhou, who died in 1999, was survived by his widow Xiao-Yi Sun and a son Andreas) world-wide rights to the fundamental VLP science, and Frazer's and Zhou's priority to invention of that fundamental VLP science, were both established.[6][21]
After 2009 reports of adverse Gardasil reactions, Frazer said "Apart from a very, very rare instance where you get an allergic reaction from the vaccine, which is about one in a million, there is nothing else that can be directly attributable to the vaccine."[27] Ian Frazer is one of the "most trusted" Australians, and some critics have accused Gardasil's advocates of exploiting patriotism[28] to promote its rapid Australian release.[29] (Australia's government had the world's most generous coverage for the drug, though it is the nation with the lowest cervical cancer mortality.)[20]
On 11 June 2012, Frazer was named a Companion of the Order of Australia (AC) for "eminent service to medical research, particularly through leadership roles in the discovery of the Human Papilloma Virus vaccine and its role in preventing cervical cancer, to higher education and as a supporter of charitable organisations."[40]
Current work
Herpes
In February 2014, it was announced that Frazer's new vaccine against genital herpes has passed human safety trials in a trial of 20 Australians. The vaccine is designed to prevent new infections.[41]
Frazer is the inaugural holder of the Queensland Government Smart State premier's fellowship, worth $2.5 million over 5 years. He has held continuous research funding from the National Health and Medical Research Council (NHMRC) since 1985, mostly relating to papilloma viruses or tumor immunology. He is currently a joint Chief Investigator on an NHMRC program grant and a NHMRC/Wellcome program grant, together worth more than $2 million a year.
^ ab"Ian Frazer". Ri Aus. Archived from the original on 10 February 2010. Retrieved 29 May 2010. Eighty per cent of Australian secondary schoolgirls have been vaccinated with Gardasil
^ ab
Whittaker, M. (4 March 2006). "God's Gift to Women". The Weekend Australian Magazine. 'Ian went to huge efforts and he got them visas to Australia,' recalls Margaret Stanley. 'It says a lot about Ian. If anything should come over in your article, it's that Ian is an extremely kind man.'
^Frazer, I. H.; Crapper, R. M.; Medley, G.; Brown, T. C.; Mackay, I. R. (20 September 1986). "Association between anorectal dysplasia, human papillomavirus, and human immunodeficiency virus infection in homosexual men". The Lancet. 328 (8508): 657–660. doi:10.1016/S0140-6736(86)90168-6. PMID2876137. S2CID34973455.
^
Frazer, I. H.; McCamish M; Hay I; North P. (3 October 1988). "Influence of human immunodeficiency virus antibody testing on sexual behaviour in a "high-risk" population from a "low-risk" city". Med J Aust. 149 (7). Lions Human Immunology Laboratories, University of Queensland, Department of Medicine, Princess Alexandra Hospital, Woolloongabba.: 365–8. doi:10.5694/j.1326-5377.1988.tb120670.x. PMID3173194. S2CID29026390.
^"A hero of women and science". Diamantina Institute at The University of Queensland. Archived from the original on 14 April 2009. Retrieved 14 September 2009. Ian Frazer was set for a career in physics when a chance encounter with an immunologist, the father of his pen-friends girlfriend, changed his course.
^
Sterling, J. C., ed. (August 2001). "1". Human Papillomaviruses: Clinical and Scientific Advances. London: Hodder Arnold. ISBN978-0-340-74215-0.
^Vaccines Forgotten Man [www.theaustralian.com.au/news/tribute-to-vaccines-forgotten-man-story-e6frg600-1111116233989]
^
Sawaya, G. F.; Smith-McCune, Karen (10 May 2007). "HPV Vaccination – More Answers, More Questions". The New England Journal of Medicine. 356 (19): 1990–1991. doi:10.1056/NEJMe078088. PMID17494932. Archived from the original on 4 January 2010. Retrieved 30 May 2010. Previous reports showed a remarkable 100% efficacy of a quadrivalent vaccine targeting HPV types 6, 11, 16, and 18 on outcomes related to vaccine HPV types in women with no evidence of previous exposure to those types [...] subgroups of subjects with no evidence of previous exposure to relevant vaccine HPV types were evaluated separately for vaccine efficacy. In these subgroups, efficacy of nearly 100% against all grades of cervical intraepithelial neoplasia and adenocarcinomain situ related to vaccine HPV types was reported [...] Why is vaccine efficacy modest in the entire cohort? One factor is the apparent lack of efficacy among subjects with evidence of previous exposure to HPV types included in the vaccine. The FUTURE II trial showed no effect of vaccination
^
Walker; J. (9 October 2005). "UQ Team Defeats Cervical Cancer". The Courier-Mail. Ian Frazer's break-through vaccine is 100 per cent effective against the most common form of the virus that causes cervical cancer, according to final-stage trial results [...] a delighted Professor Frazer, 52, said last night: 'It is very rare, almost unheard of, to achieve a 100 per cent efficacy rate in any treatment, so these results are truly wonderful.'
^
Estimates of the contemporary global mortality rate have remained in the 190,000 to 300,000 range from 2000 to 2010. The 2007 WHO progress report says that preventable cervical cancer "was responsible in 2005 for up to 500,000 new cases, and up to 257,000 deaths, more than 90% in low- and middle-income countries", but, "According to WHO’s projections, deaths from cervical cancer will rise to 320,000 in 2015 and to 435,000 in 2030" (p.4). These projections may be little effected by vaccination programs (anyway unlikely on cost grounds) because "A reduction in cancer incidence and mortality might not be measurable before 10 to 30 years after the vaccine is introduced." (p.5). Other estimates of the problem's scale are broadly in agreement:
Kennedy, F. (25 January 2006). "UQ Australian of the Year Will Continue Fight for Women's Health". UQ News. Professor Frazer said Australia and other developed nations had effective Pap smear programs to reduce the incidence of cervical cancer. 'Despite this, cervical cancer continues to be a shocking disease for women in the developed world. Women living in poverty in the developing world, where Pap smears are not widely available, account for most of the 250,000 deaths from cervical cancer each year. So this vaccine has the potential to do most good in the developing world, where it could help lift women out of poverty by relieving the burden of disease
"Transcripts – Professor Ian Frazer". Australian Broadcasting Corporation. Retrieved 29 May 2010. Ian Frazer was made Australian of the Year in 2006. He and his team at Princess Alexandra Hospital in Brisbane have developed a vaccine to beat cervical cancers that kill 250,000 women a year worldwide.
"Cervical Cancer Statistics". CervicalCancer.org. 2 March 2007. Archived from the original on 5 December 2020. Retrieved 29 May 2010. A woman dies of cervical cancer approximately every 2 minutes. In less developed countries, this type of cancer is the second most common in women and accounts for up to 300,000 annual deaths.
^ abBeran, Ruth (21 June 2006). "Ian Frazer's patent problem". Australian Life Scientist. Archived from the original on 6 April 2012. Jian Zhou died in 1999, but he was an equal partner
^
Frazer, I. (November 2007). "Correlating immunity with protection for HPV infection". International Journal of Infectious Diseases. 11. Elsevier: S10–S16. doi:10.1016/s1201-9712(07)60016-2. PMID18162240. with no breakthrough HPV infections due to waning immunity, the minimum protective anti-HPV antibody level could not be ascertained. Nevertheless, antibody titer has been used as a surrogate marker of protection in clinical trials, particularly in adolescent populations in whom efficacy studies are not feasible. (The 100% efficacious immunity is against HPV 16 and 18-related cervical cancer indicators.)
^Klein, Renate. "The Gardasil 'miracle' coming undone?". p. 1. Archived from the original on 17 October 2009. Retrieved 30 May 2010. It was only on 23–24 February 2008 that the Victorian Cytology Service ran a job advertisement for a 'newly created position' to 'help establish and operate the new National HPV Vaccination Program' (The Australian, 23–24 February 2008). That's 11 months after thousands of school girls had already received the jab.
^ ab"Queensland scientist profiles > Ian Frazer". Queensland Government. 9 February 2010. Archived from the original on 13 May 2011. Retrieved 29 May 2010. 'What is the most unusual or fun thing you've done in your job?' Being Australian of the Year and carrying the Commonwealth Games torch around Darling Harbour on a boat on Australia Day
^
Kelly, James (30 March 2010). "Vaccine doctor's good news". Stateline Queensland. ABC. Retrieved 29 May 2010. It's not exactly the same virus and therefore the vaccine we already have will not protect against that particular cancer. But the technology that we've used to develop a vaccine for cervical cancer should in principle be possible to use for prevention of some skin cancers.
^"Scientist Ian Frazer close to creating skin cancer vaccine". Brisbane Times. 16 November 2008. Retrieved 29 May 2010. If we can get encouraging results we will try and push it on as fast as we can. It's really a given that we try to focus on health problems that are significant ones.
^"Ian Frazer honoured by major Fellowship". coridon.com. 6 June 2004. Archived from the original on 12 September 2009. Retrieved 29 May 2010. I saw becoming a fellow of the AAS as recognition received towards the end of a career, whereas I see myself working in research for a lot longer yet