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Editorial: Can a Safe Vaccine be Made Using Current Strategies? Maybe not.

Can a safe anthrax vaccine be made using current strategies? Maybe Not.
By Dr. Meryl Nass

VaxGen's contract with HHS for 75 million doses of a new, purer anthrax vaccine went up in smoke in December '06. No one: not HHS, not VaxGen and certainly not FDA actually explained what the problem was. The story was that the vaccine had a "stability" problem.

Take my word for it, that was not the problem. Bioport did not even have a stability testing program of any kind until 1997. FDA lets DOD give soldiers experimental vaccines that are stored in bulk for decades with no stability test, and no expiration date. FDA is not that excited about stability.

We know the first vaccine that VaxGen tried in humans was less effective than Bioport's, as expected. Bioport's vaccine had more antigenically active molecules, and animal studies had shown such vaccines worked better than the pure PA vaccines.

Was the VaxGen vaccine safer? The systemic reaction rate was higher than Bioport's in the Phase 1 safety trial. We have no info on serious side effects. Personally, I expect that both were unsafe.

The lack of purity is unlikely to be the reason for the high adverse reaction rate. Why? Because the versions of anthrax vaccine were just as impure between 1955 and 1989, but less concentrated, and there were fewer reactions then.

VaxGen then went on to take its original vaccine and add a secret, presumably experimental adjuvant. Such adjuvants made the vaccine highly effective in animal experiments, but safety of the adjuvants had never been established.

Gulf War vets who received either UK or US (and other) anthrax vaccines developed virtually similar illnesses. Later, since 1998, the two vaccines have led to similarly high reaction rates. Both have, coincidentally, also had similar manufacturing problems.

Both the US and UK anthrax vaccines are killed vaccines. What about developing a live, attenuated vaccine? Live vaccines do not require any adjuvants, experimental or otherwise. But live animal anthrax vaccines do kill occasional animals, usually goats and llamas. This occurs either because they have not been sufficiently attenuated during manufacturing, or because the animals are susceptible to residual virulence in the vaccine strain of anthrax. They work better than killed vaccines, but are less than 100% effective. The deaths of animals have been a big enough potential problem that live vaccines for humans were never developed in the US or UK. They are used occasionally in Russia and China, but very little is known of their safety or efficacy.

Maybe the problem is the vaccine's main protective ingredient, termed "Protective Antigen." It turns out that despite the name, ProtectiveAntigen, or PA, is not so harmless.

You might expect that the main ingredient of anthrax vaccine would have been carefully studied. You would be wrong. It is eye-opening to learn there are no animal toxicity studies in the prelicensing data packet given to the US licensing authority. The vaccine was given to pregnant soldiers before it was given to pregnant mice orguinea pigs. There are still no meaningful animal toxicology studies in the literature, despite at least one expert committee recommending them several years ago. Occasionally, experimental animals being used for efficacy studies developed health problems, and the author mentioned them, but that has been the extent of the animal safety literature.

There are no recent studies in which individual ingredients, such asPA, were given to animals to learn their adverse effects.There just may be a reason for this. Government anthrax researcherswho have been around for awhile, like Arthur Friedlander, probably know what they better not find.

Back in the late 1960s, two papers were published in which PA was injected into monkeys. Blood glucose levels went down, and other blood chemistry parameters shifted rapidly. In some monkeys, allelectrical brain activity stopped for several minutes. These are very toxic reactions! PA remains biologically active, and is exerting powerful effects.

These papers were published before the original anthrax vaccine was licensed. It seemed that once the vaccine got a license, and the possibility existed that many people might receive the vaccine, the government either ceased research on adverse effects, or did it"underground" -- and never published the results. The government owned (and still owns) the patent. It also owned the equipment used to manufacture the vaccine. It owns the stockpile of vaccine.

Virtually all recipients have been government employees, and virtually all medical professionals administering the vaccine and dealing with potential adverse effects have also been government employees. Conflict of interest? Anyway, I have come to suspect that you cannot make a vaccine thatcontains a lot of PA without it causing illnesses in susceptible recipients. The Brits could not, Bioport could not, and it surelooks like VaxGen couldn't either.

The "good" news is that several other immunogenic molecules have been recently discovered from anthrax. It might be possible to construct a vaccine out of these building blocks. But so far, no one has even suggested trying this approach.

Other "good" news is that many potentially excellent drugs to kill anthrax or stop its deadly effects are in development. So treatment following exposure is going to be a lot better if there ever is ananthrax attack. Government should take some of that $877 million it snatched out of VaxGen's hands, and get these products into animal trials, as well as manufacturing small amounts in advance, as was done with VaxGen's vaccine (for a wasted $200 plus million dollars).

"Government science" may be an oxymoron these days. But come on, government scientists, you may have to take this stuff too. Please put your thinking caps on and start doing the missing studies (hint-hint: animal toxicity, and obtaining meaningful toxicity and safety data from ongoing uses of anthrax vaccines, and from the CDC anthrax vaccine clinical trial). $100 million could give you a very good idea which of the new drugs are promising, and should be subjected to human safety and surrogate efficacy trials.

For anthrax prevention, only two things are needed: a read of the1960s literature, which I have scanned into my website at thef ollowing URL:http://www.anthraxvaccine.org/problems.shtml

and the ability to think outside the current vaccine box. Why areso many policymakers wedded to a failed vaccine model?

Meryl Nass, MD