ANTHRAX: Safe, Effective Vaccine Proves Elusive

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November 6, 2001

By THOMAS D. WILLIAMS, And WILLIAM HATHAWAY
Courant Staff Writers

With four people dead from anthrax attacks in the past month and several others infected, hundreds of people are clamoring for anthrax vaccine.

Several new-generation vaccines are in the early stages of development, and a new, highly experimental rapid test for anthrax was announced by the Mayo Clinic Monday.

But only one anthrax vaccine exists in the United States, and substantial questions persist about its safety and effectiveness - and availability.

Health and Human Services Secretary Tommy G. Thompson said Monday he didn't know how many doses of the vaccine the government would need to protect laboratory, postal and emergency workers at high risk of anthrax exposure. Recently, he estimated the need at between 1 million and 5 million doses and said he thought the vaccine could be available before the end of this month.

But the manufacturer, BioPort Corp. of Lansing, Mich., remains blocked from releasing the vaccine, having failed for three years to pass federal drug production inspections. BioPort also has run low on supplies created by its predecessor, the Michigan Biologic Products Institute, from which it purchased the operation in 1998.

At present, the vaccine is authorized only for the military. And while more than half a million military personnel have been vaccinated over the past decade, hundreds have either left the military or been disciplined or court-martialed for refusing to take a vaccine that they believe poses a serious health risk.

A federal inspection is scheduled at BioPort within several weeks, but the manufacturer says it likely would be months before the vaccine could become available.

Normally, such U.S. Food and Drug Administration approvals take four to six months, said Kim Brennan Root, a spokeswoman for BioPort. Although BioPort officials have every assurance the FDA will move swiftly, she said, "It is too speculative to put a time frame on the release" of the vaccine for public use.

A Thorny History

Two weeks ago, Nancy Kingsbury, managing director of applied research for the U.S. General Accounting Office, outlined the anthrax vaccine's thorny history. Testifying before a congressional subcommittee led by U.S. Rep. Christopher Shays, R-4th District, Kingsbury said the vaccine's former manufacturer had, on several occasions in the early 1990s, altered the manufacturing process to increase production without FDA approval. Kingsbury said the changes, involving different filtering material and fermenting machinery, required testing to ensure the reconstituted vaccine's safety and effectiveness, yet that was never done.

Although the FDA approved the manufacturing changes only this year, these changes were significant, Kingsbury said. The safety data, as reported on the vaccine's cautionary label for doctors and consumers, were limited to information collected in the 1960s - three decades earlier, she said.

Service personnel who have been vaccinated over the past decade - including during the Persian Gulf War and more recently - show "a significantly greater incidence of local and systemic adverse reactions" than the ranchers and doctors who used the vaccine to protect themselves from skin contact with farm animals in the 1960s, Kingsbury said.

Current packaging for the anthrax vaccine - dating back to its original manufacturing process in the '60s - states that the adverse reaction rate is 0.2 percent. In late 1999, however, the Defense Department determined the adverse reaction rate was 5 percent to 35 percent.

A group promoting government accountability for the vaccine wrote the FDA over a year ago and demanded the vaccine's package insert warnings to reflect those new percentages; the request is pending.

The FDA is studying Kingsbury's report to see if the agency needs to address additional issues, said FDA spokeswoman Lenore Gelb.

Gelb said the FDA ensured that the vaccine was safe and effective before approving the manufacturing changes.

But Sushil K. Sharma, a GAO supervisor who helped investigate those changes, said Monday that the FDA knew about the changes long ago, and should have dealt with them immediately. He said the agency allowed service members taking the vaccine to be inoculated with "an adulterated product" - a clinical term for a product not fit for human consumption.

Jack Melling, a British researcher and former chief operating officer of a British anthrax-vaccine manufacturing firm, agreed with Sharma. Melling said the FDA gave the two successive manufacturers "a free pass," permitting violations that ordinarily would result in serious civil or criminal penalties.

Melling said if he were a postal worker, he would take the vaccine only if the risk of exposure to anthrax spores were extremely high.


Search For New Vaccines

Meanwhile, scientists are already working on safer and more effective anthrax vaccines and treatments.

For instance, AVANT Immunotherapeutics of Needham, Mass., has developed a vaccine company officials say contains fewer impurities and therefore could have fewer side effects than the BioPort vaccine.

Licensing rights to develop the vaccine have been sold to DynPort LLC, a joint venture formed by military contractor DynCorp of Reston, Va., and Porton International Inc., of Washington, D.C.

AVANT referred all questions about a timetable for developing the vaccine to DynCorp. Officials at DynCorp. referred questions to the Defense Department, which did not return phone calls Monday.

The new vaccine licensed to DynPort would, however, have one of the same drawbacks as the BioPort vaccine - it would take several inoculations to confer complete protection, said Una S. Ryan, president and chief executive of AVANT.

The BioPort vaccine is given in six shots delivered over 18 months - plus annual booster shots.

But Ryan also said the company has developed a more advanced vaccine that can be taken orally and would offer full protection after a single dose. In lab tests, she said, the vaccine has proved effective against cholera, but could be modified to protect against anthrax.

Ryan said the vaccine for anthrax could be ready for manufacture as early as January, although she acknowledged that no animal studies of the vaccine's safety and effectiveness have been conducted. Vaccines normally require extensive trials in both animals and humans.

Other companies are rushing to create treatments against toxins released by anthrax bacteria. EluSys Therapeutics Inc. in Pine Brook, N.J., uses antibodies that can bind pathogens such as anthrax toxins to red blood cells, which transport the toxins to the liver before they can damage healthy tissue.

The treatment would not confer immunity on patients, but might buy patients time for antibiotics to rid them of anthrax bacteria, company officials say. That treatment also has not been tested on anthrax.