Home' Australasian BioTechnology : Vol 26 No 2 Contents Australasian BioTechnology | Volume 26 | Number 2
In 2006, Professor Ian Frazer won the Australian
of the Year award for his research that led to the
Gardasil vaccine, which provides immunity from
some human papillomavirus (HPV) strains and
associated cervical cancers. Working with Admedus
Ltd (ASX: AHZ), Prof Frazer is now developing a
next-generation DNA vaccine technology, which,
if successful, will target and clear HPV-positive
tumour cells in people who are already infected.
Gardasil is a very effective vaccine, and take-up in Australia
has been strong, at approximately 70--75 per cent; however,
despite selling more than $1 billion annually, 2014 data out
of the United States indicates that only around 40 per cent
of that country's eligible population has been vaccinated
with Gardasil. This is also despite the 79 million people in
the United States who are infected with HPV, and the further
14 million people contracting the virus each year.
Research by the United States' National Cancer Institute
shows that high-risk HPV types cause approximately five per
cent of all cancers worldwide. In addition to cervical cancer,
HPV is believed to be responsible for 90 per cent of anal
cancers; 71 per cent of vulva, vaginal and penile cancers;
and 72 per cent of oropharyngeal cancers.
These figures, and the limited uptake of prophylactic
vaccines, have presented a great need for a therapeutic
vaccine to treat people already infected with HPV and
suffering from HPV-related cancers.
Dr David Rhodes, Admedus's chief scientific officer, says
that studies show that cancerous cells express less of the L1
protein that is key in the Gardasil vaccine. So, in developing
the patented DNA platform technology for the delivery of a
HPV therapeutic vaccine, Frazer and Admedus have optimised
a different set of HPV genes for the safe and efficient
production of antigens in the body's cells. These antigens
then stimulate the body's immune cells and alert them to its
presence, which, in turn, enables them to mount a defence
against the HPV-infected cells that carry these antigens.
Admedus has conducted several animal studies with the
HPV vaccine candidate, and has shown that the therapeutic
vaccine produces strong cytotoxic T lymphocyte (CTL)
responses. HPV-positive tumour cells were injected into
animals, and only vaccinated animals prevented tumour
growth, while non-vaccinated animals had uncontrolled
tumour growth. In more than 87 per cent of the animals,
there was no tumour 50 days post treatment. The
effectiveness of the vaccine in this challenge model is a
significant advance on published results.
Admedus is tracking towards its first HPV vaccine clinical
study this year, following the expected successful
completion of preclinical studies. As part of the Phase Ib
clinical study, the company will look at the safety of the
vaccine, as well as efficacy data in the study participants.
'Due to previous experience with the DNA vaccine platform
in other areas, this program, once initiated, was able
to rapidly progress into animal models and into formal
preclinical studies. As such, the HPV program has only been
in development for relatively few years,' says Rhodes.
Admedus believes that should the vaccine prove successful,
it will offer a simpler, more effective treatment for cervical
and other HPV-associated cancers, greatly improving the
outlook for diagnosed patients, and potentially making such
cancers a thing of the past.
The potential applications for the novel DNA vaccine
technology are promising, with indications that, alone
or in conjunction with other therapies, it may be able
to treat a range of other viruses and cancers, as well as
In addition to a HPV therapeutic vaccine, Admedus is also
using the novel DNA vaccine technology to target the herpes
simplex virus 2 (HSV-2). Admedus's HSV-2 program has
already completed a successful Phase I study in uninfected
participants, with results indicating no safety issues. And,
importantly, 19 out of 20 study participants showed a T cell
response to the vaccine antigen. This is an early indicator of
the vaccine's ability to generate an immune response.
The HSV-2 vaccine Phase II study---undertaken with the
primary outcome being assurance that the vaccine is safe
in people who are already infected with the virus---revealed
no safety issues among participating patients, according to
results released in March this year. Study participants had a
marked decrease in viral lesions (outbreaks), with a drop of
more than 90 per cent in the monthly rate versus baseline.
The average number of days HSV-2 was detected in patients
was also reduced versus baseline.
'Admedus is now on track to initiate the first clinical
study with the HPV vaccine this year after anticipated
successful completion of preclinical studies,' says
Rhodes. 'As part of the Phase Ib clinical study, the
company will look at the safety of the vaccine, as well as
efficacy data in the study participants.'
Admedus will also examine other outcomes after
vaccination, including a reduction of the symptoms and viral
flares that are related to HSV-2 lesion outbreaks and other
'Programs like Gardasil and others really show how
researchers and companies can, and must, combine
effectively to commercialise these technologies.'
Dr David Rhodes
Prof Ian Frazer
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