Posted on Sat, Oct. 29, 2005
http://www.duluthsuperior.com/mld/duluthsuperior/business/technology/13029338.htm
Big boost for anti-flu fight
TESTS SHOW CHIRON ADDITIVE MAKES VACCINE MORE EFFECTIVE
By Steve Johnson
Mercury News
A Chiron product that boosts the body's immune response to viruses may stretch
dramatically the skimpy supplies of vaccine available to combat a potential
bird-flu pandemic.
In preliminary federal tests of a Chiron vaccine reported Friday for one of the
bird-flu strains, the company's immune-system additive appeared to make the
vaccine effective in doses as little as 3.75 micrograms. That is nearly 50 times
less than the amount needed for the primary bird-flu vaccine, available from
Sanofi-Aventis of France, to be effective.
Among those encouraged by the Chiron test is Cornelia Dekker, who directs a
vaccine program at Stanford University and is on the federal government's
National Vaccine Advisory Committee.
``It's a very promising first step,'' said Dekker, who had been a research
executive at Chiron before leaving in 1997. If the additive, or adjuvant, also
significantly reduces the dose needed for the primary bird-flu vaccine, she
added, ``it would conceivably make it possible to provide more vaccine more
quickly.''
Direct comparisons between the two vaccines from Chiron and Sanofi are difficult
because they target different flu-virus strains. Sanofi's vaccine is aimed at
the virulent H5N1 virus, while Chiron's vaccine is aimed at the less prevalent
H9N2 strain.
Still, one federal health official said Friday it was likely that Chiron's
immune booster would prove equally effective when it's tested in small doses of
vaccine for the H5N1 strain in the next few months.
Although more tests are needed to confirm this, ``the data are rather
impressive,'' said Anthony Fauci, head of the National Institute for Allergy and
Infectious Diseases, the agency involved in the Chiron tests. ``It's really
quite encouraging.'' Flu vaccines work by triggering a person's antibodies to
fight the virus. Because most people have been exposed to the usual seasonal
forms of the flu, their immune systems quickly respond when they encounter it.
But because the avian flu represents a new threat to humans, experts say, it
probably will take a large dose of vaccine to stimulate an immune response,
unless a booster is added.
In the Chiron tests, the company's vaccine and its immune system additive -- the
MF59 adjuvant -- were injected into 96 people, none of whom was exposed to the
virus, said Chiron spokeswoman Alison Marquiss. The additive's effectiveness was
evaluated by measuring the test subjects' antibody responses. Chiron has been
using the MF59 adjuvant for years in its Fluad vaccine, made in Italy and sold
in Europe and other places outside the United States. It is primarily intended
to help older people with balky immune systems develop antibodies to seasonal
flu viruses, Marquiss said, adding that the MF59-bolstered vaccine has a good
safety record.
Walter Orenstein, associate director of the Emory Vaccine Center in Atlanta,
agreed. ``It represents something important,'' he said of Chiron's adjuvant.
``It's a way of trying to make more with less.''
http://www.medpagetoday.com/InfectiousDisease/URItheFlu/tb/5978
TORONTO, June 20 - An investigational oil-and-water adjuvant
for flu vaccines -- tested in conjunction with a vaccine against avian flu -- is
safe, a researcher said here. Explain to interested patients that vaccines
aimed at the H5N1 avian flu have been shown to create an immune response, but
only at very high doses, which would be a problem if they were needed to treat
large numbers of people.
Note that this study suggests an experimental oil-and-water emulsion, when used
with the vaccine can help it provide better protection at lower doses.
This study was published as an abstract and presented orally at a conference.
These data and conclusions should be considered to be preliminary until
published in a peer-reviewed publication. Tested in more than 5,000 volunteers,
the adjuvant (dubbed AS) had significantly higher rates of local and general
adverse events than a placebo, but most of them were mild, Ripley Ballou, M.D.,
of GlaxoSmithKline Biologicals in Belgium told attendees at the Options for the
Control of Influenza meeting. Rates of withdrawal in the adjuvant arm of the
randomized phase III safety trial were only 0.5% higher than in the placebo arm,
he said, mainly because of pain at the injection site that dissuaded
participants from returning for a second dose.
The issue of adjuvant safety has arisen because most of the candidate vaccines
against the H5N1 strain of avian flu require very large doses of antigen to
create an immune reaction. Use of an adjuvant could make a scarce vaccine go
further among the population-provided it was safe. A standard adjuvant,
aluminum potassium sulfate or alum, is known to be safe, but does not strongly
enhance the immunogenicity of the vaccines, so the researcher turned to an older
idea - oil and water emulsions. Dr. Ballou and colleagues randomized 5,071
volunteers (on a two-to-one basis) to get one dose of the seasonal Fluarix
vaccine without adjuvant or two 15-microgram doses of an experimental H5N1
vaccine, together with the adjuvant.
Earlier studies had already shown that even 3.5 micrograms of the vaccine,
combined with adjuvant, led to a high antibody response, Dr. Ballou said.
The researchers found that common reactions to all vaccines were significantly
higher in the H5N1 group than in the controls - redness: 38.2% versus 27.8%,
swelling: 33.1% versus 17.5%, and induration: 34.4% versus 19.1%. The incidence
of ecchymosis was 9.6% versus 5.8%. The most common general adverse effects, as
solicited by the researchers, were also higher in the H5N1 group - fatigue:
51.9% versus 30.8%, myalgia: 50.0% versus 24.6%, and headache: 46.9% versus
31.2%. The withdrawal rate in the control group was 2.52% and 3.55% in the H5N1
group. Three withdrawals in the H5N1 groups were related to a serious adverse
event (and none in the control group) but the events were not considered to be
related to the study medication.
Oil and water emulsions date back to the 1950s, according to vaccine researcher
John Treanor, M.D., of the University of Rochester Medical Center in Rochester,
N.Y. They fell out of favor because of some serious side effects, including the
development of sterile abscesses at the injection site and the suspicion - later
disproved - that they caused plasmacytomas, Dr. Treanor said. The current
generation of emulsions, on the other hand, appears not to have such serious
adverse effects, he said, and may prove valuable, especially in the event of a
flu pandemic. "I think it's quite definitive that oil and water emulsions
are very, very effective in enhancing the antibody response to neo-antigens like
a flu vaccine," he said. But researchers and clinicians still have to "think
hard about what constitutes an acceptable safety profile" for such adjuvants.
The increase in the withdrawal rate for the Glaxo adjuvant "sounds acceptable"
in a trial of 5,000 people, "but if you vaccinated a million people, that would
be 5,000 people who wouldn't come back for the second dose," Dr. Treanor said.
On the other hand, in a pandemic, people might be more willing to accept a
painful second injection, he added.
This study was supported by GlaxoSmithKline Biologicals of Belgium. Dr. Ballou
is an employee of the company.
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