VANCOUVER, British Columbia (EGMN) – Two intranasal doses of an experimental norovirus vaccine led to a relative reduction of about 45% in the incidence of acute gastroenteritis in a randomized, placebo-controlled, phase I/II challenge study.

“The vaccine protected against illness. This is the first demonstration that an intranasally delivered vaccine can prevent human illness due to an enteric pathogen,” said principal investigator Dr. Robert Atmar, a professor of molecular virology and microbiology at Baylor College of Medicine in Houston, who presented the findings.

The vaccine is a dry powder formulation of viruslike particles (VLP) that mimic the norovirus capsid. “From their first production in the early 90s, they were proposed as a candidate vaccine,” Dr. Atmar said.

The trial initially included 98 healthy adults (aged 18-50 years) who were randomized to two vaccine doses – each dose containing 100 mcg of VLP and given 3 weeks apart – or placebo.

“Just under two-thirds of the subjects had a seroresponse” to the vaccine, and “the average total rise [in norovirus antibodies] was about fourfold after two doses,” Dr. Atmar said.

About a month after the second dose, participants in the trial were administered approximately 10 human-infectious doses of norovirus and were put into a hospital setting for 4 days.

Subjects were checked daily for signs of infection, including stool virus shedding, and were monitored for signs of acute gastroenteritis. Stool was checked again at 1 and 3 weeks after the challenge.

The per-protocol analysis included 77 subjects. In all, 82% (32) in the placebo group and 61% (23) in the vaccine group developed infection, a relative reduction of 26% (P = .046); 69% (27) in the placebo arm and 37% (14) in the vaccine group developed acute gastritis, a relative reduction of 47% (P = .006).

The results were similar in the 84 subjects in the intent-to-treat analysis, with a relative reduction of acute gastroenteritis in the vaccine group of 44% (P = .005), and a nonsignificant relative reduction in infections of 22% in the vaccine group (P = .084).

“There were no severe adverse events or new onset of medically significant conditions,” in the vaccine group, Dr. Atmar said.

However, 40% had mild to moderate nasal symptoms – including runny nose, congestion, itching, sneezing, and nasal discomfort – after the first dose, and 45% after the second.

“They usually lasted only a day or so after vaccination,” Dr. Atmar said.

“Systemic symptoms were similar between the vaccine and the placebo group, and more frequently reported after the first [vaccine] dose than after the second dose. Symptoms we asked about included headache, nausea, fatigue/malaise, fever, anorexia, vomiting, and diarrhea,” he said.

The vaccine continues to be studied. Among outstanding questions is whether it protects against strains other than norovirus genogroup 1, its target. The duration of protection is also unknown, Dr. Atmar said.

An intramuscular formulation is in clinical trials, but “a commercially available vaccine is still years away,��� he said.

The study was study sponsored by the vaccines maker, LigoCyte Pharmaceuticals Inc. Dr. Atmar disclosed that he is an investigator for, and receives research support from, LigoCyte.

Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

温哥华(EGMN)——休斯顿Baylor医学院分子病毒学及微生物学教授Robert Atmar报告了一项随机、安慰剂对照的Ⅰ/Ⅱ期临床试验，结果显示双次鼻内应用诺瓦克病毒疫苗可使急性胃肠炎发病率降低约45%。该疫苗成分是一种模拟诺瓦克病毒衣壳的病毒样颗粒。这是首次报道鼻内应用的疫苗能够预防人类肠道病原体所致疾病。