Vaccine study demonstrates protection against norovirus illness

An experimental norovirus vaccine provided significant protection against both viral infection and its associated gastrointestinal illness in a study of nearly 80 subjects, said a consortium of researchers led by Baylor College of Medicine in the current issue of the New England Journal of Medicine.

"This study shows it is feasible to make a vaccine that will protect against norovirus infection and the illness it causes," said Dr. Robert Atmar, professor of medicine – infectious diseases at BCM and first author of the paper.

"Given the number of norovirus infections that occur annually and the healthcare costs associated with these infections, it is worthwhile to continue the investigation of vaccine candidates to prevent this illness caused by these viruses."

This study represents the first clinical demonstration of vaccine protection against norovirus illness. Currently, there is no specific treatment for norovirus illness other than replacing fluids and medication to help symptoms of vomiting and diarrhea, said Atmar.

The frequencies of illness and viral infection were less among the research subjects who received the vaccine than those who received a placebo or inactive medication, said Atmar.

Members of the research consortium included LigoCyte Pharmaceuticals, which developed the vaccine, and Cincinnati Children's Hospital, Johns Hopkins University, SNBL Clinical Pharmacology Center, Inc., the University of Maryland and The EMMES Corporation.

Norovirus infection is one of the most common causes of acute stomach and intestinal illness characterized by nausea, vomiting, abdominal cramps and diarrhea. The CDC estimates that approximately 21 million Americans are infected by noroviruses annually, and these viruses are an important cause of gastroenteritis worldwide. Norovirus has also been referred to as the "cruise ship virus" because of its predilection for causing outbreaks of gastrointestinal illness on these ships.

In the study, 90 healthy people aged 18 to 50 years at four sites across the country received the vaccine administered as a powder in the nose or a placebo (an inactive vaccine) in two doses. Eighty-four of them were exposed to the norovirus approximately three weeks after the second vaccination. Three weeks gave their immune system time to respond to the vaccine.

Only 37 percent of those who received the vaccine developed the stomach symptoms while 69 percent of those who received placebo developed the illness. Those who received the vaccine and became ill had less serious symptoms.

Of those who received the vaccine, 61 percent became infected with the virus versus 82 percent of those who received the placebo. The main goal of vaccination is to reduce concomitant illness, especially severe illness, associated with norovirus infection. Eleven subjects who received the vaccine were positive for infection but experienced no symptoms of norovirus illness.

Noroviruses cannot be grown in the laboratory. To get around that problem, researchers made the vaccine of virus-like particles that cannot cause infection but do activate the immune system to fight norovirus illness.

"The vaccine induced a significant immune response in 70 percent of people who received it and offered protection against both illness and infection," said Atmar. "However, it offered greater protection against illness than infection. In other words, compared to placebo recipients more persons who received the vaccine did not develop gastroenteritis, even if they were infected by the virus."

Researchers will now study whether giving the vaccine as an injection will improve the percentage of people who respond to the vaccine. They will also look at how well the vaccine can protect against strains that are less closely related to the vaccine strain, said Atmar.

This study is a proof of principle study, which means that it is performed to determine whether vaccine protection is possible. The data in the new publication confirm that vaccination is an attractive approach to address the burden of illness associated with norovirus.

"We look forward to continued development of our VLP (virus-like particle)-based norovirus vaccine candidates including additional clinical studies of our bivalent intramuscular vaccine," said Donald P. Beeman, chief executive officer of LigoCyte, the company developing the vaccine.

"The collaborative team environment at Baylor has been instrumental in moving our basic science discovery toward the clinic and these studies show for the first time that a non-replicating vaccine given intranasally can induce protection against a gastrointestinal pathogen," said Dr. Mary Estes, professor of molecular virology and microbiology at BCM, who also took part in the study. "We had been told this couldn't be done."

Others who took part in the study include Dr. David Y. Graham and Antone R. Opekun of BCM; Dr. David I. Bernstein of Cincinnati Children's Hospital; Dr. Clayton D. Harro of Johns Hopkins University; Dr. Mohammed S. Al-Ibrahim of SNBL Clinical Pharmacology Center, Inc.; Dr. Wilbur H. Chen of the University of Maryland School of Medicine; Jennifer Ferreira of EMMES Corporation; and Dr. Charles Richardson and Dr. Paul M. Mendelman of LigoCyte Pharmaceuticals.

Funding for this study came from LigoCyte Pharmaceuticals and the National Institutes of Health.