by Lay Leng TAN
The discoverer of the technology behind the first cancer vaccine believes that protection against the 25% of cancers caused by viruses will become available within 20 years.
ancer accounted for 7.6 million (13%) of all deaths worldwide in 2005. According to World Health Organization (WHO) projections, global deaths from cancer will rise to an estimated 9 million in 2015 and 11.4 million in 2030.
About one-quarter of cancer incidence arises from chronic
infection, primarily from hepatitis B viruses (liver), human papilloma
viruses (cervix), Helicobacter pylori (stomach), schistosomes
(bladder), liver flukes (bile duct), and human immunodeficiency
viruses (Kaposi sarcoma and lymphomas). Cervical cancer, the
second most common cancer among women worldwide, remains
the most common form in developing countries. In 2002, WHO
reported cervical cancer -- caused by human papilloma viruses
(HPV) -- was responsible for some 12% of all women's cancers,
or about 250,000 deaths annually. About 10 varieties of HPV are
responsible for the disease, with types 16 and 18 accounting for
more than 70% of incidence.
HPV infect up to half of women within the first five years
of their commencing sexual activity. Even though most women
naturally clear the infection, about 2% of those with the virus will
develop cancer. Pap smears effectively detect HPV and prevent
progression of the disease; however, many women, especially
those in developing countries, have no access to screening or the
How then to tackle this problem? Ian Frazer, a researcher
at the University of Queensland in Australia, has been studying
cervical cancer as a viral infectious disease and using a vaccine to
target it. He and his late colleague Jian Zhou made the discovery
in 1991 that led to the development of the vaccine 15 years later
in conjunction with the Australian biomedical company CSL Ltd
and international pharmaceutical company Merck & Co.
For this landmark work, Frazer was named Australian of the
Merck markets the vaccine under the brand name Gardasil.
GlaxoSmithKline (GSK) has developed its own version, Cervarix,
with technology licensed from the University of Rochester in New
York State and from CSL Ltd.
Gardasil, a prophylactic HPV vaccine, prevents viral infection.
The vaccine protects against HPV types 16 and 18 as well as genital
warts. Administered in three shots over a period of six months,
it provides life-long immunity. The cost varies from country to
country: in Australia, the full course costs A$460, in the US about
US$360, and in Singapore about S$600.
In Australia, 20,000 women out of a population of 20 million
undergo cervical surgery to forestall getting cervical cancer every
year. The high 1-in-1000 incidence has spurred the government to make Gardasil freely available to all girls from 12 to 26 in 2007
and 2008, after which it will scale down the programme to those
in the 12ĘC13 age group.
The high price tag arises from the vaccine's complexity: it
comprises four vaccines, making it many times more expensive
to make than, say, the hepatitis B vaccine. The complicated
fermentation technology and process -- making virus-like particles,
breaking them up, cleaning them, putting them back again
-- pushes up manufacturing costs.
Frazer has worked with the Gates Foundation and the WHO's
Expanded Vaccine Initiative to help make the drug available as
cheaply as possible in the developing world. His team is researching
the optimal age for receiving it and the best delivery system in
Scientists recommend that vaccinated women continue to
undergo regular Pap screening as other types of HPV may still
cause cervical cancer. Gardasil does not render any protection to
Can researchers modify the vaccine to treat the infection?
Frazer's team is conducting a clinical trial using virus-like particles
without adjuvant on a group of infected people, and they expect to
have the results in late 2008. The Australian group also collaborates
with doctors in Wenzhou and Shinjiang in China, researching a
therapeutic vaccine against HPV-caused genital warts and cancers
such as recurrent respiratory papillomatosis in children.
HPV shows no evidence of being subject to any selection
pressures. If scientists can develop a drug to kill HPV type 16,
the most virulent, no other more potent variety will replace it.
Studies of sex workers in Scandinavia suggest that each type of
HPV infection has no impact on the others.
Frazer, founder and director of the Centre for Immunology and
Cancer Research at the Princess Alexandra Hospital in Brisbane,
Australia, reveals that his lab is working on a vaccine for hepatitis
C virus, which causes liver cancer. The group chose hepatitis C
because a proven need exists for the vaccine. Evidence suggests
that the particle technology used against HPV might work for
hepatitis C as well.
Vaccines prevent infection by producing antibodies against
proteins and protective mechanisms on the virus's surface. HPV,
a very simple virus with no defences, provides a relatively easy
target. The ones difficult to penetrate are such viruses as herpes
and HIV bristling with defences against the immune system.
Frazer believes that vaccines against all these viruses will be
available in 20 years' time. Although he admits that no perfect
vaccine against HIV will exist because of the virus' chameleon-like
defences, a vaccine 50% effective is better than none.
A vaccine against hepatitis C has to be almost 100% effective
whereas that against Epstein-Barr virus (EBV) must prove fully
100% effective. Most children with this virus do not get sick and usually get rid of it naturally; only 1% of cases will develop into
cancer. Delayed infection is generally associated with more severe
disease. Thus the vaccine must lick the EBV completely to be
Frazer explores extending to other diseases the recombinant
technology by which he makes virus-like particles -- such as
arboviruses (arthropod-borne viruses) that cause dengue fever and
Japanese encephalitis. The challenge does not lie in the technology
but rather on successful vaccine application, he explains. When
a person who has earlier contracted dengue has another attack,
the symptoms exacerbate. A vaccine may further aggravate
the situation if it provides only partial immunity to some viral
serotypes -- the patient will worsen or even die when exposed to
a new serotype, especially as this re-exposure can lead to dengue
haemorrhagic fever. "We really have to make sure the vaccine will
prevent the disease it seeks to prevent," he cautions.
According to Frazer, the opportunity for vaccine improvement
comes from novel adjuvants that render vaccines more powerful
for better immunity. For instance, new adjuvants developed by
GSK appear to boost and prolong the immune response to the
vaccines such as hepatitis B to which they have been added.
Another technological trend takes the form of recombinant
DNA and viruses. The scientist bets on DNA vaccine as the
next-generation preventive treatment. Walking the talk, he cofounded
Coridon, an Australian start-up company with platform
technologies for developing DNA therapies.
Frazer expects that big pharmaceutical companies initially
will be reluctant to adopt new DNA immunotherapies, should
they prove effective, because of their commitment to their
current technology and the desire to avoid competing with their
existing products. However, he believes competition and consumer
demand will propel these companies into using the most effective
technology and processes when the next-generation vaccines
come on-line. Such a move will improve global healthcare as
vaccination represents the most effective public health measure
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