U.S. war on anthrax has its risks - Rush to stock new vaccine has scientists wary
By Peter Gorner
Tribune science reporter
Some scientists are questioning a U.S. government plan to spend as much as $1.4 billion on an unlicensed, experimental anthrax vaccine to be stockpiled in case bioterrorists attack American cities.
Although the vaccine has been tested in animals, testing in humans is in its early phases and the vaccine has not yet demonstrated its effectiveness, making the purchasing plan premature, according to critics.
But the Bush administration, as a follow-up to its promise to have enough smallpox vaccine on hand for every American, said it hopes that within two years the country will have sufficient quantities of the new anthrax vaccine to inoculate 25 million people.
That, along with the storage of antibiotics that already have proved their effectiveness against anthrax spores, could serve as countermeasures against a feared biological agent.
"As the lead federal agency for public health and medical response, we are moving forward to ensure our nation is protected against anthrax," said Tommy G. Thompson, secretary of the Department of Health and Human Services.
But an anthrax expert, Dr. Meryl Nass, of Bar Harbor, Maine, cautioned that the public "should not be misled that this vaccine is an improvement to the currently licensed vaccine.
"This one is definitely more pure, but unfortunately its purity has not been shown to improve safety or effectiveness," said Nass, a former government consultant who led the campaign against the existing vaccine after getting reports from military personnel of mystifying and serious side effects.
After a terrorist attack, the U.S. plan calls for the entire population of a city to be inoculated with the new vaccine, while also taking antibiotics until immunity develops.
After that, with regular booster shots, people theoretically would be immune to anthrax, even if spores lingered for years, as they have been shown to do.
Nass said that most "shocking" is the government's contention that the new vaccine would enable cities contaminated with anthrax to be habitable.
`Most bogus thing'
"Where's the science behind that? It's the biggest, most bogus thing of all," she said.
The only currently licensed anthrax vaccine in the U.S. is a mixture of proteins produced by a weakened form of Bacillus anthracis, the bacterium that causes the deadly disease in animals and people.
Developed for animal-hide workers in the 1950s and used primarily by the military, the vaccine requires six injections over 18 months and has been associated with severe side effects.
The licensed anthrax vaccine became the subject of bad publicity and litigation because of the Pentagon's insistence on mandatory vaccination of troops. The vaccine's reputation never recovered.
During the anthrax-letters panic of 2001, nearly all of the postal workers at risk refused the vaccine when it was offered.
Nonetheless, some skeptics are questioning what they perceive as the rush by the government to buy several million doses of the new vaccine, called rPA102, before clinical trials are completed and its safety and effectiveness evaluated.
Also being questioned is the choice of the main manufacturer, VaxGen Inc. of Brisbane, Calif., a company whose AIDS vaccine failed inclinical trials in 2003.
"Once again, VaxGen has managed to leverage few scientific data to capture a significant amount of federal dollars," said Dr. Steven Wolinsky, an AIDS researcher and chief of the division of infectious diseases at the Feinberg Medical School at Northwestern University.
"Most of us in the scientific community agree there is meager scientific evidence to support this effort. As a clinician, I would not offer the vaccine to people exposed to anthrax spores without providing them with concomitant drug treatment."
More promising anthrax vaccines are in the pipeline, but they may fail to attract commercial developers because the government already has made up its mind, some experts contend.
They also warn of another potential anthrax vaccine boondoggle that would make the legal, medical and ethical disputes over the existing vaccine, BioThrax, pale by comparison.
Bidding will close April 16 on a contract for 75 million doses of the rPA102 vaccine that is expected to be awarded to VaxGen and Avecia Ltd, a privately held company based in Manchester, England.
According to the Department of Health and Human Services, "the new vaccine has already shown to be stronger and more effective than the vaccine being used today. It will require fewer doses per individual to provide immunity against the effects of anthrax inhalation."
The firms already have contracts--VaxGen for $80.3 million and Avecia for $71.3 million--to each produce 3 million doses and conduct human trials to test the vaccine.
The new vaccine is a purified protein designed to stimulate the body to produce antibodies to neutralize the most dangerous part of anthrax--called protective antigen, or PA.
"The way anthrax works is that one part attaches to your cell and the other part [the protective antigen] gets flipped on the inside to have the toxic effect," said Dr. Craig E. Smith, representing the Bioterrorism Work Group of the Infectious Diseases Society of America.
"This vaccine stimulates antibodies that destroy the attachment component so the toxic part can't get into where it needs to do its dirty work. It just gets washed out of your system without any problem," Smith said.
"If a bomb blew up and the cloud spread anthrax through the city, we could follow the cloud and vaccinate the 2 million people downstream who may take weeks to months to manifest the disease."
Smith called the new vaccine "a no-brainer. A win-win situation."
VaxGen recently reported that the first phase of human testing--with 100 volunteers age 18 to 49--showed that antibody responses to higher doses of rPA102 conferred protection within the same range as the existing vaccine.
Dr. Harry L. Keyserling, professor of pediatrics at Emory University School of Medicine, conducted the clinical trial with colleagues from St. Louis University and Baylor and Johns Hopkins Universities.
Local reactions, mainly arm pain, were more common with the old vaccine, but short-lived systemic reactions, mostly headache and fatigue, were more than twice as common (39 percent versus 18 percent) with the new vaccine.
"Side effects were mild, nothing that would interfere with everyday activity. Further studies will continue to monitor reactions and adverse effects," said VaxGen spokeswoman Kesinee Yip.
But systemic reactions worry some specialists because long-term effects of the vaccine are virtually unstudied and initial systemic reactions--reactions away from the injection site--could put people at high risk of chronic illness later.
Linked to problems
Published case reports have linked anthrax vaccine to a host of problems including chronic fatiguing illnesses, chronic pain syndromes and endocrine and autoimmune disorders.
Another top government official insisted the new vaccine purchase plan is not precipitous and "was all done in a very measured, careful way.
"There were multiple contracts doing the research to show that it was safe and stimulated the immune system against anthrax. Now comes the production capabilities to put it in place," said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases.
"We now have enough smallpox vaccine to handle anything. But with anthrax vaccine, we had a gap," Fauci said.
"We didn't have enough vaccine if, indeed, we had an attack on a city. Nor did we have enough to vaccinate first responders and others who might be doing the cleanups after an attack of anthrax."
As with the current vaccine, the new vaccine was developed by bioweapons specialists at the U.S. Army Medical Research Institute of Infectious Diseases at Ft. Detrick, Md. They successfully tested the vaccine for years in primates, officials said.
"Almost two years ago, we started a strategic plan for developing countermeasures to high-risk agents--smallpox, anthrax, tularemia, plague, botulism toxins and the hemmorhagic fevers. This purchase is part of that," Fauci said.
Others challenge that assertion, however.
"The primary ingredient, PA [protective antigen] has significant toxicity. Since no immediate need exists, and testing has not been completed, why rush to order a huge stockpile of such a vaccine?" asked Nass."VaxGen is only at the Phase 1 stage, pre-efficacy testing. Why buy a huge amount of a product before the manufacturer has showed it will work?
"Many things are dropped much later as a result of Phase 3 testing--like VaxGen's AIDS vaccine. Nothing should be purchased in bulk at this very early stage of testing," Nass said.
Tribune science reporter
Some scientists are questioning a U.S. government plan to spend as much as $1.4 billion on an unlicensed, experimental anthrax vaccine to be stockpiled in case bioterrorists attack American cities.
Although the vaccine has been tested in animals, testing in humans is in its early phases and the vaccine has not yet demonstrated its effectiveness, making the purchasing plan premature, according to critics.
But the Bush administration, as a follow-up to its promise to have enough smallpox vaccine on hand for every American, said it hopes that within two years the country will have sufficient quantities of the new anthrax vaccine to inoculate 25 million people.
That, along with the storage of antibiotics that already have proved their effectiveness against anthrax spores, could serve as countermeasures against a feared biological agent.
"As the lead federal agency for public health and medical response, we are moving forward to ensure our nation is protected against anthrax," said Tommy G. Thompson, secretary of the Department of Health and Human Services.
But an anthrax expert, Dr. Meryl Nass, of Bar Harbor, Maine, cautioned that the public "should not be misled that this vaccine is an improvement to the currently licensed vaccine.
"This one is definitely more pure, but unfortunately its purity has not been shown to improve safety or effectiveness," said Nass, a former government consultant who led the campaign against the existing vaccine after getting reports from military personnel of mystifying and serious side effects.
After a terrorist attack, the U.S. plan calls for the entire population of a city to be inoculated with the new vaccine, while also taking antibiotics until immunity develops.
After that, with regular booster shots, people theoretically would be immune to anthrax, even if spores lingered for years, as they have been shown to do.
Nass said that most "shocking" is the government's contention that the new vaccine would enable cities contaminated with anthrax to be habitable.
`Most bogus thing'
"Where's the science behind that? It's the biggest, most bogus thing of all," she said.
The only currently licensed anthrax vaccine in the U.S. is a mixture of proteins produced by a weakened form of Bacillus anthracis, the bacterium that causes the deadly disease in animals and people.
Developed for animal-hide workers in the 1950s and used primarily by the military, the vaccine requires six injections over 18 months and has been associated with severe side effects.
The licensed anthrax vaccine became the subject of bad publicity and litigation because of the Pentagon's insistence on mandatory vaccination of troops. The vaccine's reputation never recovered.
During the anthrax-letters panic of 2001, nearly all of the postal workers at risk refused the vaccine when it was offered.
Nonetheless, some skeptics are questioning what they perceive as the rush by the government to buy several million doses of the new vaccine, called rPA102, before clinical trials are completed and its safety and effectiveness evaluated.
Also being questioned is the choice of the main manufacturer, VaxGen Inc. of Brisbane, Calif., a company whose AIDS vaccine failed inclinical trials in 2003.
"Once again, VaxGen has managed to leverage few scientific data to capture a significant amount of federal dollars," said Dr. Steven Wolinsky, an AIDS researcher and chief of the division of infectious diseases at the Feinberg Medical School at Northwestern University.
"Most of us in the scientific community agree there is meager scientific evidence to support this effort. As a clinician, I would not offer the vaccine to people exposed to anthrax spores without providing them with concomitant drug treatment."
More promising anthrax vaccines are in the pipeline, but they may fail to attract commercial developers because the government already has made up its mind, some experts contend.
They also warn of another potential anthrax vaccine boondoggle that would make the legal, medical and ethical disputes over the existing vaccine, BioThrax, pale by comparison.
Bidding will close April 16 on a contract for 75 million doses of the rPA102 vaccine that is expected to be awarded to VaxGen and Avecia Ltd, a privately held company based in Manchester, England.
According to the Department of Health and Human Services, "the new vaccine has already shown to be stronger and more effective than the vaccine being used today. It will require fewer doses per individual to provide immunity against the effects of anthrax inhalation."
The firms already have contracts--VaxGen for $80.3 million and Avecia for $71.3 million--to each produce 3 million doses and conduct human trials to test the vaccine.
The new vaccine is a purified protein designed to stimulate the body to produce antibodies to neutralize the most dangerous part of anthrax--called protective antigen, or PA.
"The way anthrax works is that one part attaches to your cell and the other part [the protective antigen] gets flipped on the inside to have the toxic effect," said Dr. Craig E. Smith, representing the Bioterrorism Work Group of the Infectious Diseases Society of America.
"This vaccine stimulates antibodies that destroy the attachment component so the toxic part can't get into where it needs to do its dirty work. It just gets washed out of your system without any problem," Smith said.
"If a bomb blew up and the cloud spread anthrax through the city, we could follow the cloud and vaccinate the 2 million people downstream who may take weeks to months to manifest the disease."
Smith called the new vaccine "a no-brainer. A win-win situation."
VaxGen recently reported that the first phase of human testing--with 100 volunteers age 18 to 49--showed that antibody responses to higher doses of rPA102 conferred protection within the same range as the existing vaccine.
Dr. Harry L. Keyserling, professor of pediatrics at Emory University School of Medicine, conducted the clinical trial with colleagues from St. Louis University and Baylor and Johns Hopkins Universities.
Local reactions, mainly arm pain, were more common with the old vaccine, but short-lived systemic reactions, mostly headache and fatigue, were more than twice as common (39 percent versus 18 percent) with the new vaccine.
"Side effects were mild, nothing that would interfere with everyday activity. Further studies will continue to monitor reactions and adverse effects," said VaxGen spokeswoman Kesinee Yip.
But systemic reactions worry some specialists because long-term effects of the vaccine are virtually unstudied and initial systemic reactions--reactions away from the injection site--could put people at high risk of chronic illness later.
Linked to problems
Published case reports have linked anthrax vaccine to a host of problems including chronic fatiguing illnesses, chronic pain syndromes and endocrine and autoimmune disorders.
Another top government official insisted the new vaccine purchase plan is not precipitous and "was all done in a very measured, careful way.
"There were multiple contracts doing the research to show that it was safe and stimulated the immune system against anthrax. Now comes the production capabilities to put it in place," said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases.
"We now have enough smallpox vaccine to handle anything. But with anthrax vaccine, we had a gap," Fauci said.
"We didn't have enough vaccine if, indeed, we had an attack on a city. Nor did we have enough to vaccinate first responders and others who might be doing the cleanups after an attack of anthrax."
As with the current vaccine, the new vaccine was developed by bioweapons specialists at the U.S. Army Medical Research Institute of Infectious Diseases at Ft. Detrick, Md. They successfully tested the vaccine for years in primates, officials said.
"Almost two years ago, we started a strategic plan for developing countermeasures to high-risk agents--smallpox, anthrax, tularemia, plague, botulism toxins and the hemmorhagic fevers. This purchase is part of that," Fauci said.
Others challenge that assertion, however.
"The primary ingredient, PA [protective antigen] has significant toxicity. Since no immediate need exists, and testing has not been completed, why rush to order a huge stockpile of such a vaccine?" asked Nass."VaxGen is only at the Phase 1 stage, pre-efficacy testing. Why buy a huge amount of a product before the manufacturer has showed it will work?
"Many things are dropped much later as a result of Phase 3 testing--like VaxGen's AIDS vaccine. Nothing should be purchased in bulk at this very early stage of testing," Nass said.
