LB-2. An Intramuscular (IM) Bivalent Norovirus GI.1/GII.4 Virus Like Particle (VLP) Vaccine Protects Against Vomiting and Diarrhea in an Experimental Human GII.4 Oral Challenge Study
Session: Oral Abstract Session: Late Breaker Oral Abstracts
Saturday, October 5, 2013: 10:42 AM
Room: The Moscone Center: 102 (Gateway Ballroom)
Background:

Noroviruses (NoVs) are the leading cause of acute gastroenteritis across all age groups, with GII.4 as the most commonly detected genotype. The goals of a successful norovirus vaccine are to provide protection against medically significant illness and to reduce transmission and outbreaks.  

Method: :  We conducted a randomized, double blind, placebo-controlled, multicenter trial of a bivalent NoV G1.1/GII.4 VLP vaccine adjuvanted with Monophosphoryl Lipid A (MPL, GlaxoSmithKline) and alum. At least 28 days after two IM vaccinations (28 days apart), healthy adults aged 18-50 were challenged with 4000 RT-PCR genome equivalents of a heterologous GII.4 NoV, isolated for 4 days as inpatients, and monitored for acute gastroenteritis illness. Stool samples were collected at days 1-4, 10 and 30 post-challenge to test by RT-(real time) PCR for challenge virus, and sera were collected pre- and day 30 post-challenge to test for anti-NoV antibodies.

Result:

109 subjects were challenged (vaccine N=56), placebo N=53). In the per protocol population (50 vaccine, 48 placebo), 56.1% of challenged subjects (52.0% vaccine, 60.4% placebo) were infected with the challenge virus (by NoV RT-PCR positive stool). With respect to illness, no cases of severe vomiting and/or diarrhea were recorded in the vaccine group vs 4 cases in the placebo group (0.0% vaccine vs 8.3% placebo, 100% reduction, p=0.054).  Fewer vaccinees reported moderate or severe diarrhea or vomiting (6.0% vs 18.8% placebo, 68.0% reduction, p=0.068). Vomiting and/or diarrhea of any severity was significantly reduced by the vaccine (20.0% vaccine vs 41.7% placebo, 52.0% reduction, p=0.028). Fewer vaccinees shed norovirus at day 10 after challenge (22.4% vs 36.2% placebo, 38.1% reduction p=0.179). The primary composite endpoint (reduction of any type of gastroenteritis and norovirus case ascertainment by either of 2 analytical assays) was not met possibly because the illness definitions and analytical assays lacked the ability to differentiate infection or disease. Secondary endpoints of reduction of disease severity were met.

Conclusion:

The bivalent VLP NoV vaccine provided protection against vomiting and/or diarrhea, and will be taken forward into field efficacy studies.

David I. Bernstein, MD, MA1, Robert L. Atmar, MD2, Marshall Lyon, MD3, John J. Treanor, MD4, Wilbur H. Chen, MD5, Robert Frenck, MD1, Xi Jiang, PhD1, Jan Vinje, PhD6, Mohamed S. Al-Ibrahim, MB, ChB7, Jill Barrett, MPH8, David Y. Graham, MD9, Charles Richardson, PhD10, Robert Goodwin, PhD10, Astrid Borkowski, MD11, Ralf Clemens, MD, PhD11 and Paul M Mendelman, MD10, (1)Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, (2)Medicine, Baylor College of Medicine, Houston, TX, (3)Emory Univ, Atlanta, GA, (4)University of Rochester Medical Center School of Medicine and Dentistry, Rochester, NY, (5)Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, (6)Centers for Disease Control and Prevention, Atlanta, GA, (7)SNBL Clinical Pharmacology Center, Inc., Baltimore, MD, (8)The EMMES Corp, Rockville, MD, (9)Baylor College of Medicine, Michael E. DeBakey VAMC, Houston, TX, (10)Takeda Vaccines (Montana), Bozeman, MT, (11)Takeda Vaccines, Zurich, Switzerland

Disclosures:

D. I. Bernstein, LigoCyte Inc: Investigator and receives royalties for a different norovirus vaccine, Research support

R. L. Atmar, Takeda Vaccines: Investigator and Scientific Advisor, Research grant

M. Lyon, Ligocyte: Investigator, Research support

J. J. Treanor, University of Rochester: Investigator, Research support

W. H. Chen, None

R. Frenck, None

X. Jiang, LigoCyte Pharmaciutics: Consultant and Grant Investigator, Consulting fee, Licensing agreement or royalty and Research support

J. Vinje, None

M. S. Al-Ibrahim, None

J. Barrett, None

D. Y. Graham, LigoCyte: Investigator, Grant recipient and Licensing agreement or royalty

C. Richardson, takeda Vaccines Montana: Employee and Shareholder, Salary

R. Goodwin, Takeda: Employee, Salary

A. Borkowski, Takeda: Employee, Salary

R. Clemens, Takeda: Employee, Salary

P. M. Mendelman, Takeda Vaccines (Montana): Employee, Salary

Findings in the abstracts are embargoed until 12:01 a.m. PST, Oct. 2nd with the exception of research findings presented at the IDWeek press conferences.