Click here: Anthrax vaccine report shows spikes in potency

Friday, November 2, 2001

San Francisco Chronicle

Amid pressure to vaccinate civilians at risk for anthrax, evidence has emerged that unauthorized changes in the vaccine manufacturing process before the Gulf War may have radically boosted the potency of the controversial shots. Veterans groups and armed services personnel have complained that the anthrax vaccine is unsafe, and they say the new evidence lends credence to their view. Researchers at the Army's biological warfare defense lab found as much as a 100-fold increase in the concentration of the anthrax vaccine's active ingredient in batches produced after a switch to new filters in 1990. The previously unpublished report was uncovered by investigators of the General Accounting Office, which has been studying the complaints from veterans and military personnel. The GAO released its findings last week. "Somebody ought to look at this question as we go forward to approve this vaccine," said Nancy Kingsbury, managing director for applied research at the GAO. The national Centers for Disease Control and Prevention has recommended that 800 lab technicians who are processing suspected anthrax samples receive the vaccine. It is also considering a recommendation that postal employees who work near high-speed sorting machines receive the vaccine.

RISKS NOT UNDERSTOOD

Whether higher concentrations of the active ingredient could be harmful is still unknown, investigators say. The active ingredient, known as protective antigens, are particles from a dead anthrax bacteria that are used to stimulate the immune system to produce antibodies. Although the antigens train the body's immune system to attack anthrax bacteria, there can be too many of them. "Overstimulation of the immune system in certain respects can lead to immunological disorders," said Dr. Jack Melling, formerly head of Britain's anthrax vaccine program and a consultant to the GAO. Vaccine critics said the report bolsters suspicions by veterans that the anthrax vaccine they took in 1990 is somehow related to Gulf War Syndrome, the symptoms of which include chronic pain, skin rashes, nausea, memory loss and concentration problems.

OPPOSITION TO VACCINES

Current efforts by the Pentagon to vaccinate 2.4 million military personnel have run into stubborn opposition by soldiers, sailors and airmen who maintain that a disproportionate number of those taking the shots have suffered dangerous side effects. Army Spc. Sandra Larson of Spokane died of aplastic anemia after taking the sixth shot in the series that makes up the vaccine. Last week, her family filed suit against vaccine maker Bioport Corp., of Lansing, Mich., alleging that the vaccine is at fault. The company maintains that the vaccine is no more dangerous than childhood vaccines used against diphtheria and whooping cough.

PRODUCED BY PRIVATE FIRM

Bioport is a private company that acquired rights to anthrax vaccine manufacturing in 1998 from Michigan Department of Public Health, which had been making it since 1970. Until the Gulf War, it was used primarily by laboratory workers and veterinarians who might be exposed to the rare disease. Kingsbury's report, delivered to the House national security subcommittee last week, also describes how the Michigan Department of Public Health, under contract with the Pentagon, changed both the reactor vessels in which the vaccine is made and the filters with which it is refined -- without FDA approval. In fact, the U.S. Food and Drug Administration knew nothing about the switch from ceramic to nylon filters -- which boosted production in 1990 -- until GAO investigators informed the agency in December 2000. The changes, including two subsequent switches of nylon filters in 1996 and 1997, were approved after the fact by the FDA only last July. "This conforms with what we have seen in the past, that the producers played pretty fast and loose with the recipe," said Lawrence Halloran, counsel to the national security subcommittee chaired by Rep. Christopher Shays, R- Conn.

FDA SAYS VACCINE IS CONSISTENT

Despite concerns raised by the GAO, the FDA contends that nearly a decade of records show the vaccine composition has been consistent. "The FDA reviewed all potency data results from pre-1990 through 1998 and detected no changes in potency testing results throughout the time period in which filters were changed," said FDA spokeswoman Lenore Gelb. At the same time, the FDA has forbidden Bioport from shipping its vaccine since 1998, citing a variety of quality control problems. Kim Brennen Root, spokeswoman for Bioport, said yesterday that the vaccine is safe. "The GAO continues to spend time and resources looking for a smoking gun. There is no smoking gun," she said. But Russell Dingle, an American Airlines pilot who resigned from the Connecticut Air National Guard rather than take required anthrax shots, said the GAO report underscores how a succession of anthrax vaccine makers flouted rules designed to assure safe medicines. "The military had determined in 1991 that the changes they had made increased the potency 100-fold. The FDA did not know about it until we told them," Dingle said. The GAO turned the 1990 Army study over to the FDA last week. "We are reviewing it," said the FDA's Gelb.

CONCENTRATION VARIES

A copy of the document obtained by The Chronicle shows that the concentration of protective antigen varied substantially among the 19 batches studied by scientists at USAMRIID, the Army biological warfare defense lab at Fort Detrick, Md. The highest concentration of active ingredient recorded in a batch before the change in filters was 20.6 micrograms per milliliter. That is nearly 100 times the lowest level in the series, 0.23 micrograms per milliliter, using the older filter. USAMRIID could not be reached for comment. However, in Kingsbury's report to Congress, she acknowledges that they explained that the results of their work "should be interpreted cautiously," because the testing method used at the time was new -- although it is widely accepted today. Lt. Col. John Gravenstein, deputy director of the Pentagon's Anthrax Vaccine Immunization Program, said service personnel should be reassured that the shots are safe. "The nation's best biological scientists are at the FDA, not the GAO," he said.

ANTHRAX PROTECTION

Veterinarians, livestock handlers, wool mill workers, anthrax researchers and military personnel are vaccinated for anthrax. Immunization is achieved with six shots over a period of 18 months. Then an annual booster shot is needed. . A combination of three toxic antigens makes anthrax lethal. One of them, Factor II, the "protective" antigen, is used in the vaccine because it is the necessary link that makes the combination lethal. Ê

The vaccine

The vaccine is made from a strain of anthrax that does not cause the disease but does produce protective antigens. The vaccine contains no whole bacteria, dead or alive. How it works - When the vaccine is injected, the Factor II antigen is taken up by white blood cells, which use it to create antibodies. Protection - The immune system now stores copies of the antibody, so the body is ready if it comes into contact with anthrax. Vaccine makeup - The vaccine is called Anthrax Vaccine Adsorbed because the active ingredient, Factor II antigen, is adsorbed, or attached to aluminum hydroxide particles, to be more easily taken up by the body. Water makes up 99% of the vaccine, along with trace amounts of preservatives. Factor I antigen - With Factor II creates fluid buildup and swelling. Factor III antigen - With Factor II produces some lethal effects. Factor II antigen - When combined with both Factor I and Factor III, an overwhelmingly lethal toxin is formed.

Sources: Bioport; Department of Defense; Reuters; New York Times John Blanchard / The Chronicle

E-mail Sabin Russell at srussell@sfchronicle.com