By Mary Welch

Antex Biologics Inc. said Phase II testing confirmed its Campylobacter vaccine is safe, effective and produces an immune response.

Theresa Stevens, vice president of corporate development for Gaithersburg, Md.-based Antex, said the company expects to file a new drug application in three to five years.

"We suspected that the vaccine offered protection against Campylobacter but, until we did our human trials, we didn't know," Steven said.

In the U.S., Campylobacter jejuni is the leading cause of food-borne illness, which causes gastroenteritis and diarrhea, including a severe form of traveler's diarrhea. Worldwide, 400 million to 500 million cases of diarrhea appear annually. When combined with pneumonia, diarrhea causes half of the deaths of children under the age of five. Guillain-Barre syndrome, an acute paralytic illness, may follow Campylobacter infections. About 5,000 cases of the syndrome are reported in the U.S. each year.

Campylobacter is mostly spread in infected chicken meat and studies suggest that 70 to 90 percent of U.S. chicken now carry the bacteria. It has become increasingly resistant to antibiotics, because of their widespread use to treat chickens.

Antex's vaccine consists of inactivated bacterial cells produced by its patented Nutriment Signal Transduction (NST) technology. NST is the ex vivo simulation of the in vivo environment, to produce bacterial vaccines that are identical to the infectious bacteria that cases diseases in humans.

Technology Tricks Body's Immune Defenses

"We take the inactive cells grown in the NST and we grow cells that mimic the infected organisms," Stevens said. "They trick the body's immune system into thinking they are live bacteria that going to cause an infection, but they're not."

The current Phase II trial consisted of two stages. In the first, 28 people were given various concentrations of live bacteria to determine the amount required to cause an illness in at least 70 percent of the volunteers. Measured were occurrence, time of onset and duration of signs and symptoms including, diarrhea, fever and enteritis.

During this stage, the immune response to the Campylobacter infection was gauged. Those results yielded data that seemed to prove what had been surmised in preclinical trials with animals, Stevens said.

Specifically, the results demonstrated that the vaccine induced Campylobacter-specific hormonal and cellular immune responses, including an interferon-gamma (INF-gamma) response, as well as local intestinal and systemic antibody output. INF-gamma production typifies a Th1-type T-cell response, which indicates active cell-mediated immunity. Eighty-six percent of the patients exhibited vaccine-specific INF-gamma responses, and 58 to 63 percent had vaccine-specific IgA or IgG antibody secreting cells in their blood following vaccination.

The trials showed that the vaccine-specific INF-gamma responses, along with the production of local intestinal IgA antibodies directed against Campylobacter, offered the strongest defense, Stevens said. In fact, 71 percent of the volunteers protected against illness had increased INF-gamma and intestinal IgA antibody responses, as opposed to only 28 and 24 percent, respectively, of the unprotected individuals.

Previously infected patients, when reintroduced to the bacteria, showed the same immunological responses as the other protected volunteers.

"We didn't have the markers to show what dosage offered the protection but it is clear there is a correlation," Stevens said.

The second part of the test indicated that the participants showed little or no reaction to the vaccine, which was administered in liquid form with two doses two weeks apart. Future trials will test whether, by altering the dosage, the vaccine can be given one week apart or three weeks apart, with the vaccine's strength changing. The vaccine will be tested in pill or capsule form as well.

Collaborating with Antex on vaccines in a deal worth up to $30 million is SmithKline Beecham plc, of London. (See BioWorld Today, Nov. 6, 1997, p. 1.) *