July 8, 2002

WILL THREE UNLICENSED SMALLPOX VACCINES BE USED TO IMMUNIZE 500,000 AMERICANS?

By Meryl Nass, MD

An estimated 500,000 first responders, lab and hospital workers will receive smallpox vaccine, the Department of Health and Human Services (DHHS) announced yesterday.

This is an interesting announcement, because to my knowledge there exist no FDA-licensed smallpox vaccines.

There are three vaccine candidates whose safety and efficacy are uncertain at this time.

The first vaccine made available was named Dryvax, which was pulled out of storage after approximately thirty years. Initial reports indicated that a 1:5 dilution yielded 70% efficacy. However, recent reports indicated that this diluted old vaccine was nearly 100% effective.

Which is it?

Furthermore, a 1999 report in Science noted that the rubber seals on the vials were deteriorating, and that 1/4 of the vials "were suspect." Are the suspect vials being diluted to make new vaccine also?

The second vaccine comes from the Aventis stockpile, allegedly "lost" for decades. Millions of doses of vaccine do not get lost. Vaccine lots are required to have a documented testing history, and both the manufacturer and FDA should have records on file of the dates the lots were released and their specifications at the time.

For both these ancient vaccine stockpiles, there exists no approved method by which FDA can legally "relicense" them for current use based on test results generated today. There is no way long-expired product can be "regenerated" for licensure within current FDA regulations.

The third vaccine candidate is the Acambis (previously Oravax, using Baxter as subcontractor) smallpox vaccine. This is a new vaccine whose makeup, as well as its safety and efficacy profile, have not been publicly discussed. The FDA finalized a rule May 30, 2002 for accepting animal tests in lieu of human tests for efficacy of bioterrorism drugs and vaccines. This opens the door for the new vaccine to receive a full FDA license.

An article in this month's Emerging Infectious Diseases (CDC) by James LeDuc and Peter Jahrling et al indicates that the Acambis vaccine is in Phase I trials and licensure is not expected until sometime in 2003.

When will the public and medical professionals learn all the details needed to make an informed decision about using this new product? This information is not releasable by FDA until after licensure. One hopes that the vaccine will not be used until adequate safety testing has taken place: Phase I trials do not provide thorough information on drug and vaccine safety.

It thus appears that three unlicensed vaccines may soon be available for use in 500,000 Americans. Potentially severe consequences are anticipated in those with eczema, HIV infection, other forms of immune deficiency, and cancers (who are receiving radiation or chemotherapy). There may be other, unknown risk factors that predispose to serious vaccine complications.

The anticipated extent of spread of the vaccinia virus to contacts of the 500,000 has not been publicly discussed, nor have measures to minimize such spread, although taking such steps is a very important part of protecting the health of contacts. Recall that most of the 500,000 are involved in direct patient care: their contacts are the very people most at risk of vaccinia's spread.

Are the 500,000 expected to acquiesce to receiving an experimental vaccine(s)? Will they be asked to sign an informed consent, and will the consent ask them to give up any rights to compensation for injuries sustained as a result of vaccination? Will they be placed into clinical trials comparing the three vaccine candidates? Who will pay for deaths and injuries to these vaccine recipients that occur as a result of vaccination? Who will pay for deaths and injuries in their contacts?

Does it make good sense to perform this experiment with all our nation's first responders and a sizable chunk of our lab techs and physicians? Or does it make more sense to start vaccinations slowly and observe closely for problems, so they can be mitigated prior to vaccinating large numbers of critical personnel?

I am a primary care physician with a hospital practice, and I may be one of the designated half million. I daresay that if offered the vaccine, I will not be a "taker". How many of the 500,000 intend to comply with this DHHS directive?