How do you test that a human Ebola vaccine works? You don't

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DARocksMom

Wed, 29 Sep 2004 08:15:12 EDT

 

 

An Uncertain Defense / How do you test that a human Ebola

vaccine works? You don't

 

 

http://www.sciam.com/article.cfm?chanID=sa006 & articleID=000B0B7E-6C63-1150-ABF

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An Uncertain Defense

 

How do you test that a human Ebola vaccine works? You don't

By W. Wayt Gibbs

 

 

 

The Ebola virus is among the deadliest on earth; in outbreaks

last year in the Republic of Congo, 157 of the 178 people infected

with it died of hemorrhagic fever. Because it can be exceedingly

contagious in aerosol form, the Ebola virus ranks with smallpox and

anthrax as one of the most worrisome potential biological weapons.

Although there is no effective treatment, recent tests have shown a

new vaccine able to prevent infection in monkeys.

 

Clearly, researchers could never intentionally expose human volunteers

to the lethal virus. And there are no populations at especially

high risk for Ebola, as there are for HIV. So how can doctors

determine whether the vaccine works in people?

 

That question, which applies as well to experimental vaccines for

smallpox and anthrax, took on new significance on July 21, when

President George W. Bush signed the Project Bioshield Act. The law

authorizes the U.S. Department of Homeland Security to spend up to

$5.6 billion over 10 years to increase its stockpile of antibioweapons

medicines, including drugs that the U.S. Food and Drug Administration

has not yet approved as safe and effective.

 

 

 

The secretary of health and human services can now recommend that the

president order the distribution of experimental drugs to the armed

forces or even to the general populace, should the secretary perceive

" a significant potential for a domestic emergency, involving a

heightened risk of attack. "

 

Although scientific evidence of some kind must suggest that the

drugs will do more good than harm, human clinical trials--for decades,

the only evidence that has mattered--are no longer strictly required.

 

The prospect of treating thousands of people with a vaccine or drug

only proved to work on animals may seem risky. But the realities of

the pharmaceutical market and the lethal character of many bioweapons

leave few alternatives. The pharmaceutical industry has already all

but abandoned work on vaccines for many of the world's major

infectious diseases, such as malaria and tuberculosis, because the

people most vulnerable to such illnesses tend to be least able to

afford expensive medicines.

 

There is virtually no natural market for vaccines to prevent smallpox

(which has been eradicated) or anthrax (which is not contagious) or

Ebola (which occurs in vicious but sporadic outbreaks).

 

 

So federal agencies are creating a market. " The Project Bioshield law

specifies initial stockpiling of Ebola vaccine at about $90 million

and a long-term procurement of about $260 million, " Vijay B. Samant,

president of Vical, observed in an August conference call with

investors. Vical is a biotech firm based in San Diego; both it and

Crucell, a Dutch company, have won potentially lucrative contracts to

manufacture the genetically engineered ingredients in the new vaccine.

 

 

" To gain FDA approval, we will have to gather safety data on perhaps

5,000 people, " says Gary J. Nabel, director of the Vaccine Research

Center at the National Institutes of Health. Nabel's group designed

the immunization to have two stages: a DNA primer and a viral booster

shot. Both parts contain only minute fragments of Ebola virus, so the

vaccine itself could not cause infection. Small human safety trials of

just the primer portion, made by Vical, are now under way at the NIH.

 

But recent experiments on macaques have shown that the booster alone

led to full immunity against Ebola in less than four weeks. Jaap

Goudsmit, chief scientific officer at Crucell, says it remains to be

seen how long the protection will last.

 

 

That is a question typically answered by a large-scale clinical trial.

But a special rule passed in 2002 allows FDA approval even without

direct evidence that it works in humans, in cases where subjecting

humans to clinical trials would be unethical or infeasible.

 

 

A company must first show that the vaccine works in monkeys (or

another animal similar to humans). Researchers then have to figure out

how the animals' immune systems respond to the optimal dose and find

an equivalent dose in humans that generates a similar immune response.

 

Project Bioshield allows the president to waive even that lowered

regulation when the nation faces " heightened risk of attack. "

 

 

It may be years before scientists can determine an optimal human dose

for the new Ebola vaccine. That does not mean, however, that it won't

soon enter the national stockpile. The Bush administration says that

next year it expects to purchase 75 million doses of a new anthrax

vaccine that has not yet even completed human safety trials.

 

 

Of course, Nabel says, " you can bet there would be follow-up studies

if the Ebola vaccine was used in a real outbreak. " He acknowledges,

however, that " if the vaccine is so good that it aborts infection

before the virus induces an immune response, we might not be able to

tell who was exposed and who wasn't. "