Vaccines With A Sci-Fi Ring

Biotechnology companies are closing in on new ways to vaccinate with a glass of transgenic milk for malaria, a banana for hepatitis, even Star Trek-like nasal sprays and "gene guns."

This sci-fi innovation promises not only to ease the 15 vaccine shots an average child gets by age 4, but to lower production costs and allow protection against diseases that conventional vaccines simply can't tackle.

"Vaccines will be more than just dead pathogens injected in your arm," Gregory Milman, pathogenesis chief at the National Institute of Allergy and Infectious Diseases, said Monday.

Most are still in early development, he cautioned. But companies backed by millions of dollars in new National Institutes of Health funding are developing everything from edible vaccines to vaccines made of disease DNA simply shot through people's skin cells with needleless hyposprays. "It's very exciting technology," Milman said.

Aviron Inc. will ask the Food and Drug Administration later this year to approve the first of these novel vaccines, a nasal-spray flu vaccine for children, who are the main spreaders of influenza. Aviron is completing testing in adults, and reports that FluMist is more than 90 percent effective.

It doesn't just take the ouch out of flu shots. Injections only produce antibodies against flu in patients' bloodstreams, while a nasal spray produces a powerful but different reaction mucosal immunity inside the nose where influenza strikes, Aviron President J. Leighton Read told some 4,000 scientists and companies at the biotechnology industry's annual meeting here.

"Someday we may be able to deliver all vaccines via mucosal surfaces" like the nose or gastrointestinal tract, said Dr. Myron Levine of the University of Maryland, who is helping develop what he calls "vaccine cuisine."

Plants can be genetically engineered to grow with an antigen against human disease inside them. The idea: Eat the plant and be vaccinated. The concept just won legitimacy when the first human experiment showed people who ate raw potatoes with a diarrheal vaccine showed a protective immune response.

Raw potatoes aren't exactly appetizing, and any raw produce will rot before enough people can be vaccinated, said Iain Cubitt of Britain-based Axis Genetics PLC.

But California researchers recently discovered they could cook potatoes grown with cholera antigen without destroying the medicinal spuds. Now Axis is working on vaccines against diarrhea and hepatitis B that it foresees selling in preserved foods like pureed bananas for babies, dried tomatoes or banana chips. That way, doctors can carefully control the vaccine dose, Cubitt said.

Growing complex antigens inside living creatures can be far simpler than synthesizing them in huge factories, said Harry Meade of Genzyme Transgenics, which breeds goats and cows with special genes so they produce drugs in their milk.

Now the company is working with NIH to milk a alaria vaccine. Scientists think a protein called MSP-1 is vital for malaria protection but until now couldn't synthetically produce enough to test. Genzyme essentially built a gene that produced the protein, bred mice with that gene, and found the mice secreted the protein in their milk. If it proves effective, goats would be bred to produce the vaccine, Meade said.

"Our goal is to use transgenic dairy animals as bioreactors," he explained.

People might one day actually drink vaccine milk, some experts predicted, but Meade said the animals make a cheap factory, too pulling vaccine antigens out of transgenic milk could cost a fraction of conventional vaccine manufacturing.

But the newest technology would let the human body manufacture its own vaccine. Called DNA vaccines, scientists would inject people with small DNA fragments from a disease. Somehow, body cells absorb this DNA and let it manufacture the protein needed for immune protection. So far, it has worked mostly in animals, cautioned Dr. Margaret Liu of Chiron Corp., but a handful of early attempts against the AIDS virus found people show signs of an immune response. Some HIV vaccines are in Phase II testing, and companies are seeking DNA vaccines against flu, hepatitis and herpes.

Companies hope to use Star Trek-like hyposprays as "gene guns" to send DNA vaccines through skin pores without a needle. One company is creating a helium-driven gun that promises to drive DNA particles into the skin faster than the speed of sound.

"We have a lot of work to do," Liu stressed. But if it works, simply culling DNA "would let us target diseases ... that today are unconquered."

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