MERYL NASS, MD

NOVEMBER 7, 2002

NEW ANTHRAX VACCINES

From The Frying Pan Into The Fire?

By Meryl Nass, MD

The NIH has contracted with two private companies for a new anthrax vaccine for civilians. Twenty-five million dollars has been allotted for this in the current federal budget. The Pentagon contracted with Dynport Corporation for a new military anthrax vaccine. Implicit in these negotiations is the recognition the existing vaccine has to go.

The new vaccines will be based on recombinant protective antigen (rPA) and be much purer than the current vaccine. In order to improve on the existing vaccine, it is essential to know what is wrong with the current product. But the only problems openly acknowledged are short-term, annoying reactions, and the need for too many doses. No published studies have explored what it is about the vaccine that causes problems.

What do we know about rPA vaccines for anthrax?

1. They are purer, so certain side effects are likely to be less
2. In the past, similar vaccine candidates have been less immunogenic than the currently licensed vaccine: this means they may need more doses
3. They may require new adjuvants to boost the immune response, in order to make them effective
4. These adjuvants have not so far been licensed by FDA for use in humans, due to safety concerns
5. They can be manufactured with lot-to-lot consistency
6. They contain no spore antigens, though research done in France suggests these antigens should be included because they significantly boost efficacy (1)

Harvard professor John Collier spoke to the Committee on Government Reform on February 28, 2002 about new approaches to anthrax. He described his dominant negative mutant of protective antigen (PA), and he claimed in a recent Scientific American that PA on its own, without lethal or edema factor, is entirely nontoxic (2).

Professor Collier’s assertion that PA lacks toxicity was dead wrong. In the 1960s, prior to licensing the current anthrax vaccine (whose main ingredient is PA), at least two studies done at Fort Detrick looked at the effect of PA, in the absence of lethal factor or edema factor, injected into monkeys.

In the first study, levels of blood glucose and liver glycogen dropped markedly with injection of PA (3). In the second study, PA was injected into the monkeys’ cerebrospinal fluid. The authors had the following to say: "Within 30 to 60 seconds, a marked decrease in cortical [brain] electrical activity was noted, followed in some animals by complete electrical silence at approximately 3 to 5 minutes (4)."

Therefore, relying on recombinant PA for a "second generation" anthrax vaccine could result in a vaccine with increased serious side effects and less effectiveness. Similarly, the PA "dominant negative mutant" and other anthrax treatments that rely on PA may turn out to be highly toxic in man.

It is critical to explore these issues before the government embarks on new vaccine and treatment strategies about which it still knows very little.

READINGS

1. Brossier F, Levy M, Mock M. Anthrax spores make an essential contribution to vaccine efficacy. Infect Immun 2002 Feb;70(2):661-4.

2. Young JAT and Collier RJ. Attacking Anthrax. Scientific American, March 2002. 36-45.

3. Walker JS, Lincoln RE and Klein F. Pathophysiological and Biochemical Changes in Anthrax. Federation Proceedings 1967; 26 (5): 1539-44.

4. Vick JA, Lincoln RE, Klein F et al. Neurological and Physiological Responses of the Primate to Anthrax Toxin. J Infectious Diseases 1968; 118 (1): 85-96.