Wall Street Journal - December 24, 2002
Marilyn Chase, Staff Reporter of The Wall Street Journal

German researchers report successful animal tests of a milder smallpox vaccine that is believed to carry less risk of death and severe illness than the conventional vaccine. Separately, two American biotechnology companies in the Boston and San Francisco Bay areas said they plan to develop and test potentially safer vaccine candidates that could be ready for public use as early as 2004.

Natural smallpox was eradicated world-wide in 1980, and the U.S. stopped vaccinating in 1972. But fears of a bioterror attack led the Bush administration this month to revive the country's long-abandoned immunization program with vaccinia, an old vaccine that is effective but causes an array of serious side effects, including death in one to two people for every million people vaccinated. A large segment of the population -- including young children and people whose immunity has been weakened by AIDS, chemotherapy or other conditions -- is currently barred from receiving the vaccine.

Gerd Sutter, a virologist at Germany's National Center for Environment and Health in Munich, says he used a milder smallpox vaccine known as modified vaccinia Ankara, or MVA, to protect mice against a lethal exposure to a virulent strain of vaccinia. Vaccinated animals lived, while control animals died within eight days. In addition, Dr. Sutter describes, in Tuesday's Proceedings of the National Academy of Sciences, a new method for evaluating immune-response levels evoked by different vaccine strains that could aid clinical trials.

"I believe MVA is a serious candidate for a next-generation smallpox vaccine," Dr. Sutter said in an interview. In the mid-1970s, he said, MVA was used to safely immunize about 150,000 German citizens who were considered at high risk from the conventional vaccine due to conditions such as the skin rash, eczema. By that time, however, the U.S. had stopped routine vaccination, so MVA was never developed here.

Now, MVA is at the center of a major federally sponsored clinical trial.

Last Thursday, at the National Institutes of Health in Bethesda, Md., an unidentified volunteer became the first of 105 Americans to test MVA made by Therion Biologics Corp. of Cambridge, Mass.

The clinical trial will evaluate the safety of MVA in healthy volunteers age 30 and younger who have never been vaccinated against smallpox.

Another goal is to compare the immune responses elicited by MVA with those elicited by Dryvax, the currently approved smallpox vaccine in the U.S.

The trial will also assess whether vaccination with MVA can protect against another pox virus.

In Cambridge, Mass., Therion's chief scientific officer, Dennis Panicali, said it has been working on MVA for more than six years as a viral vehicle for an AIDS vaccine, and recently began to investigate its use against smallpox itself.

In German studies, 10% or fewer people developed fevers from MVA, compared with between 60% and 70% of people who received standard vaccinia, said Barney Graham, chief of the clinical trials unit of the Vaccine Research Center of the National Institute of Allergy and Infectious diseases, an NIH unit. Dr. Graham said he hoped to see some trial results as early as next summer.

Therion's Dr. Panicali cautioned that it will be at least a couple of years before its MVA vaccine is commercially available in this country.

In Brisbane, Calif., VaxGen Inc., a vaccine company long associated with efforts to develop an AIDS vaccine, has thrown its hat into the smallpox arena with a Japanese partner. VaxGen said it entered into an initial agreement with the Chemo-Sero-Therapeutic Research Institute of Japan, also known as Kaketsuken, to pursue clinical development and seek regulatory approval of a smallpox vaccine called LC16m8.

Made from another mild strain of vaccinia known as the Lister Clone, LC16m8 is the result of culture and selection methods that isolated a strain that cannot infect brain cells -- thus removing the cause of one major type of vaccine injury: vaccinia encephalitis, a potentially devastating inflammation that can cause brain damage, retardation or death.

Japan vaccinated about 50,000 children with the Lc16m8 vaccine in 1974 without major side effects. Studies of 10,000 people showed 7.7% experienced fevers, compared with 25% of people who had fevers after getting standard smallpox vaccine, said Donald Francis, VaxGen's co-founder and president.

Clinical trials should start in the first half of 2003, he said. "The hope is we could do this by 2004, but that's very rapid."

Write to Marilyn Chase at marilyn.chase@wsj.com

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