By Joe Fiorill
Global Security Newswire
BALTIMORE — A top U.S. vaccine development official today expressed hope that
President George W. Bush would sign the Project Bioshield initiative into law by
month’s end but called the absence of such a law unimportant to the
project’s progress (see GSN, May 20).
Bioshield is designed to guarantee a
government market for vaccines that drug makers otherwise would see as unprofitable and be
reluctant to produce.
The Senate and House of Representatives
have passed separate versions of legislation to enact Project Bioshield, but no step has
yet been taken to reconcile the chambers’ approaches and allow passage by the full
Congress. Bush, who first proposed the project early last year, would be expected to
quickly sign the bill if congressional passage occurred.
Despite Bioshield’s statutory
nonexistence, Congress has appropriated funds for the project, a fact stressed today by
top Health and Human Services Department vaccine adviser Philip Russell during a
question-and-answer period after a speech he delivered at the University of Maryland Law
School.
“The latest rumor was that Congress
would probably act and the president would sign it at the end of this month. I hope
so,” said the former head of the Walter Reed Army Institute of Research and the
Army Medical Research and Development Command.
Russell said Health and Human Services
could be expected to begin spending appropriated funds within months irrespective of
Congress’ progress on the legislation.
“It really isn’t holding us
up,” Russell said of the congressional delay. He said proposals already
issued would “hopefully” result in the award of a contract for vaccine
production by August or September.
Officials have said the first contract
likely to be awarded under Bioshield would be for an anthrax vaccine (see GSN, June 8). Russell today placed such a vaccine among
top priorities for the project, along with anthrax treatments, a
“next-generation” smallpox vaccine, botulinum antitoxin, recombinant plague
vaccine and other products.
Russell also underlined the danger of
development of dangerous antibiotic-resistant biological agents. “We have about
five years to find a first-class solution to that problem,” he
said, mentioning mass vaccinations as one such fix.
WASHINGTON POST
U.S. to Buy Anthrax Vaccine
Stockpile Would Permit Mass Inoculations
By Justin Gillis
Washington Post Staff Writer
Friday, March 12, 2004; Page A01
The government is preparing to buy enough
experimental anthrax vaccine for 25 million people, a stockpile that would permit mass
inoculations in numerous U.S. cities if terrorists launched a broad assault with the
deadly germ.
The new vaccine would be the most significant
addition to the national anti-terrorism stockpile since the Bush administration fulfilled
a pledge to buy enough smallpox vaccine for every citizen of the United States. Up to now,
there has been little commercial incentive for companies to develop a modern anthrax
vaccine, but the new plan would change that, creating a reserve big enough in a year or
two to immunize everyone in the New York and Washington metropolitan areas -- or in other
cities that might be targeted in an anthrax attack.
Two biotechnology companies, in California and in
Britain, have won contracts to make an early stockpile of the unlicensed vaccine
sufficient to inoculate 2 million people, according to bidding documents released
yesterday, and they are likely to bid soon on larger contracts. Coupled with the
government's successes in stockpiling smallpox vaccine and antibiotics, the anthrax
purchases mean the United States will soon have developed a wide array of defenses against
the two most important biological weapons.
"The colleagues that I work with in this
business would tell you that smallpox and anthrax are the two most-feared agents, and
we've done a lot to take those off the table," said Michael T. Osterholm, director of
the Center for Infectious Disease Research and Policy at the University of Minnesota, who
has advised the federal government on combating bioterrorism. He said a large-scale attack
"would still be a tragic situation, but compared to what we had available two years
ago, we have come a long, long way."
Government scientists are still discussing how the
anthrax vaccine might be used, and how it compares with other drugs under development,
such as artificial antibodies given over the short term to prevent or treat anthrax
infection. But the documents released yesterday show the government has decided to order
an additional 75 million doses, enough to vaccinate at least 25 million people. Added to
the 2 million doses already on order, as much as 9 percent of the country's population
would be covered.
The stockpile is projected to cost at least $700
million on top of nearly $200 million already spent, a congressional report said. The two
companies involved, VaxGen Inc. of Brisbane, Calif., and Avecia Ltd. of Manchester,
England, are racing to scale up their factories for rapid vaccine production.
The most likely use of the vaccine, experts said,
would be to inoculate the entire population of a city immediately after a terrorist
attack. People might need to take antibiotics for several weeks to prevent disease until
the vaccine kicked in, but after that they would be immune even if anthrax spores lingered
in the city for years, as the germs are believed capable of doing.
While preventive vaccination of entire cities isn't
likely any time soon, said Anthony S. Fauci, director of the National Institute of Allergy
and Infectious Diseases, inoculations may be considered for some high-risk occupational
groups, including the hazardous-materials teams that would respond to an anthrax attack.
"If the safety profile of this vaccine is as
good as we think it's going to be, I think there's going to be at least a discussion among
some of the unions of postal workers," he said. Two postal workers in Washington died
in 2001 after letters containing anthrax spores were sent through the mail.
The new vaccine is designed to be a potent, highly
purified replacement for an existing anthrax vaccine, a product developed in the 1950s
that is used mostly by the Pentagon to inoculate troops.
http://www.washingtonpost.com/wp-dyn/articles/A51691-2004Mar11.html
- 1. Apart from the 2001 smallpox vaccine
fiasco, no entity has ever before contracted for nearly a billion dollars' worth of
untested drug or vaccine. Let's explore the Sept-Nov 2001 smallpox contract first.
- * Soon after DHHS contracted with Acambis
for a total of 209 million doses of smallpox vaccine, it came to light that the US
actually had a stockpile of smallpox vaccine of between 85 and 105 million doses.
- * It also turned out that the old vaccine
had been tested in college students at various dilutions, and a 20% (1 in 5) dilution
yielded as much protection as full strength vaccine. Thus the existing US stockpile was
sufficient to vaccinate at least 400 million people before any additional vaccine was
purchased. However, that did not stop DHHS from purchasing nearly a billion dollars of new
vaccine, which used the identical virus strain that was in the older vaccines.
- 2. The Acambis smallpox vaccine (209 million
doses ordered before this recombinant vaccine had even been created) is unlikely to ever
be used, barring a smallpox epidemic, since it employs the same vaccinia virus strain that
caused a number of cardiac problems and several deaths in the 38,000 civilian health care
workers vaccinated. (It did the same in military troops, who are still receiving it, but
those deaths have been covered up--I had a letter published in JAMA [2003;290:2123-4]
about this.) A less reactogenic smallpox vaccine was also ordered by DHHS, for people who
were not expected to tolerate the original vaccine. However, only 15 million doses of this
vaccine, called modified Ankara, were purchased.
- 3. Acambis's VP Tom Monath was shown by
Judith Miller in the August 7, 1998 NYT to have misrepresented himself as a CDC employee,
rather than a private vaccine developer, in a meeting with President Clinton in which he
pushed hard for production of bioterrorism vaccines. Why did DHHS contract for smallpox
vaccine with a small unknown company that had been so tarred?
- 4. VaxGen (another start-up that is likely
to get some or all of the DHHS recombinant anthrax contract) similarly has been
investigated by the London Times and The Guardian for improper manipulation of its stock
price, has faced several lawsuits by investors, pulled out of a Thai AIDS vaccine trial
when close to completion, leaving its partners very unhappy, and to my knowledge has never
brought a product to market. Why contract with VaxGen to produce a vaccine created a
number of years ago at Fort Detrick? (I am aware that VaxGen has so far only received $80
million from DHHS for 3 million doses, but is anticipated to get a much larger contract
for some or all of 75 million doses.)
- 5. Vaxgen's own head to head trial of its
rPA (recombinant protective antigen) anthrax vaccine versus the licensed Biothrax/AVA
vaccine showed the recombinant vaccine had over twice the systemic adverse reaction rate
(39% vs 18%) as the original. Yet Vaxgen claimed it compared favorably in terms of safety.
- 6. The WP article is correct in that
"many" postal workers refused AVA in 2001-2: 99% to be exact.
- 7. Effectiveness testing of anthrax vaccine
in animals cannot predict human effectiveness. Vaccine effectiveness varies all over the
map depending which experimental animals are chosen. And no correlates of protection have
been identified yet that permit extrapolation from animals to humans. In fact, in older
studies from the 1980s and 1990s performed at Fort Detrick and Porton Down, UK, rPA
vaccines were LESS effective in animal models than the currently licensed vaccines.
- 8. Why rush to order this huge stockpile,
which according to DHHS is not expected to be available until two years after the contract
is signed, when the vaccine shows no strong evidence of being either safe or effective in
humans? There exists no immediate need. Is someone afraid that complete testing will show
up its flaws?
- 9. Is the reason for purchasing now, before
testing is complete and licensing assured, to head off development of more promising
approaches, such as Human Genome Sciences' privately developed monoclonal antibody
ABThrax, which reported very positively on an early clinical trial last week, and derail
development of other drugs that are cheaper, more effective than vaccine and only need be
given after an actual exposure, not before?
- 10. Lest anyone be misled that this vaccine
is an improvement on the currently licensed anthrax vaccine, it was selected because it
had been developed a number of years ago at Fort Detrick but never used, ie it happened to
be available when the government decided to replace the existing anthrax vaccine. It is
definitely more pure, but unfortunately its purity has not been shown to improve safety or
effectiveness. There is no good reason for it to require fewer doses either. In fact, its
primary ingredient, PA (protective antigen) has been demonstrated to have significant
toxicity. For example, injecting it into the cerebrospinal fluid of monkeys caused
complete cessation of brain electrical activity for several minutes, in studies performed
at Fort Detrick in the 1960s, but these studies may not have been reviewed by those
involved with vaccine contracting.
- Meryl Nass, MD
- Moount Desert Island Hospital
- Bar Harbor, Maine 04609
- H 207 276-5092
- W 207 288-5082 ext 220 or pager 441
