Copycat. Viruslike particles mimic the norovirus's structure to trigger an immune system response.

LigoCyte Pharmaceuticals Inc.

Stomach Bug Vaccine in the Pipeline?

The next time a "stomach flu" has you sprinting for the bathroom, take heart: A vaccine may be on its way. Based on the results of a new clinical trial, the experimental vaccine is highly effective against a strain of norovirus—the bugs that may be responsible for over 90% of the stomach upsets collectively known as gastroenteritis.

According to the Centers for Disease Control and Prevention (CDC) in Atlanta, noroviruses cause an estimated 21 million cases of vomiting and diarrhea in the United States every year. In developing countries, infections cause an estimated 200,000 deaths annually in children under age 5. The virus is transmitted chiefly by food, water, or unwashed hands that have been contaminated by the feces of an infected person. Noroviruses are often called the "cruise ship virus": Outbreaks are common in confined living quarters, including military bases and hospitals. Nursing homes are hot spots as well; the virus is a particular threat to the elderly.

Developing a vaccine has been a research challenge. "Noroviruses can't be grown in culture and don't infect laboratory animals," notes clinical virologist Robert Atmar of Baylor College of Medicine in Houston, Texas. A breakthrough came in the early 1990s, when the Norwalk virus, a strain of norovirus, was cloned in the laboratory of molecular virologist Mary Estes, also at Baylor. Estes found that when a certain key protein from the virus was produced in cultured cells, the protein assembled itself into "viruslike particles" (VLPs) that could produce a strong immune system response in laboratory animals. The discovery led LigoCyte Pharmaceuticals of Bozeman, Montana, to license and develop its own line of VLPs, which mimic the virus's structure closely enough to rouse the body's immune system against the virus but do not contain any material that allows the virus to reproduce.

A VLP-based vaccine sharply reduced both the rate of infection and the severity of symptoms, as shown by the clinical trial led by Atmar, Estes, researchers from LigoCyte, and from three other test centers. Ninety healthy volunteers received either the vaccine or a placebo as a nasal spray in two doses 3 weeks apart. Participants were then admitted to one of the four test hospitals, where they drank a potent viral concoction and waited.

About 80% of participants in the placebo group became infected with the virus (as measured by the antibodies in their blood), but only about 60% of the vaccinated group did. Symptoms appeared in 69% of the placebo group but in only 37% of the vaccine group. Symptoms in the vaccinated group were also less severe and developed more slowly. (The 20% of uninfected, placebo-treated subjects were probably immune from previous exposure, Atmar explains.) Results of the trial are reported today in The New England Journal of Medicine.

"This is a proof-of-concept study, the first to show that a vaccine can be effective against noroviruses," Atmar says. Additional studies, he says, are needed to monitor the vaccine's success in a less-controlled setting—a military base or nursing home, for example. Atmar adds that whether the vaccine will confer protection against more than one strain of norovirus is still unknown. LigoCyte is currently conducting a trial of an injected form of the vaccine that works against two different virus types.

Virologist Jan Vinjé of CDC calls the results of the new study encouraging. "It's a very safe vaccine since it contains no viral genetic material," he says. "A good next step would be to see whether the vaccine generates enough of an immune response to provide protection in elderly patients," he adds, noting that the vast majority of outbreaks occur in long-term care facilities.