Laird Harrison

September 11, 2012

September 11, 2012 (San Francisco, California) — A new vaccine against norovirus infection showed promising results in a small clinical trial, researchers reported here at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy.

"There was a rapid response to the first dose," said first author John Treanor, MD, professor of medicine at the University of Rochester in New York.

No serious adverse reactions were attributed to the vaccine, which quickly produces antibodies against one of the most common strains of the virus.

It is estimated that norovirus, the leading cause of foodborne disease, causes half the gastroenteritis in the world, Dr. Treanor said. There is currently no vaccine against the virus, and no medicine that combats it in an infected person.

Because the study was a preliminary phase of investigation, it measured only adverse events and biomarkers of immunity; it did not test how well subjects could resist a norovirus infection.

"The very next step is to look at whether this vaccine has the ability to protect against a challenge, then increase the sample size, because it was too small to draw conclusions," Dr. Treanor told Medscape Medical News.

Still, after receiving a liquid intramuscular injection of the vaccine, subjects produced more antibody titers against the virus than did subjects in a previous trial of a nasal powder formulation, said Dr. Treanor. Both formulations are being developed by Ligocyte Pharmaceuticals of Bozeman, Montana.

Both formulations feature the company's virus-like particle (VLP) approach, in which vaccines mimic the external structure of proteins in the external coats of viruses but do not contain any virus RNA, so they cannot cause infection.

"One of the challenges of controlling these viruses with vaccines is their multiple genotypes," Dr. Treanor noted.

In this trial, researchers tested a vaccine designed to resemble some of the strains causing the most illness.

They combined 50 µg of a VLP based on the genogroup I, genotype 1 (GI.1) Norwalk strain of the virus with 50 µg of a VPL based on 3 strains from the Yerseke, Den Haag and Houston genogroup II, genotype 4 (GII.4) variant.

The VPLs were adjuvanted with monophosphoryl lipid A (GlaxoSmithKline) 0.05 mg and aluminum hydroxide 0.5 mg.

The researchers randomly assigned 73 patients to receive 2 doses, administered 4 weeks apart, of either the vaccine or a saline solution.

Dr. Treanor and his colleagues used enzyme-linked immunosorbent assays (ELISAs) to measure norovirus antibodies prior to vaccination and on days 7, 21, 28, 35, and 56 after vaccination. They also measured antibody persistence 6 and 12 months after vaccination.

Injection-site pain and tenderness were the most common symptoms reported. No fever or serious adverse events deemed to be related to the vaccination were reported.

The geometric mean antibody titers against the GI.1 VLP increased 118-fold in subjects 18 to 49 years of age, 83-fold in subjects 50 to 64 years of age, and 24-fold in subjects 65 to 85 years of age.

A second dose did not increase the antibody titers.

Elevations in antibodies from baseline in subjects 18 to 49 years persisted on day 393 after vaccination, by 19-fold to GI.1 and by 3.4-fold to GII.4, as measured by the ELISA.

The researchers plan further assays, including other ELISA assays, histo-blood group antigen-blocking assays, and hemagglutination-inhibition antibody assays.

Session moderator Jan Bonhoeffer, MD, assistant professor of infectious disease and vaccine at the University Children's Hospital in Basel, Switzerland, was surprised by the lack of fever reported in the study subjects. "To me, [fever] is not an adverse event but a sign of developing immunity," said Dr. Bonhoeffer.

Dr. Treanor responded that fever would not be expected with this type of vaccine. However, he noted that a patient's response could depend on previous exposure to norovirus. "The very rapid response to the first dose is an indication that mostly we are dealing with a recall response," he said.

Dr. Treanor reports that he is a grant investigator for Pfizer and a research contractor for Ligocyte Pharmaceuticals, GlaxoSmithKline, Protein Sciences, and Sanofi. Dr. Bonhoeffer has disclosed no relevant financial relationships.

52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): Abstract G-1048. Presented September 10, 2012.

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