717. Phase 1 Dosage Escalation, Safety and Immunogenicity Study of a Bivalent Norovirus VLP Vaccine by the Intramuscular Route
Session: Poster Abstract Session: Vaccine Studies, Adjuvants, and Discovery
Friday, October 21, 2011
Room: Poster Hall B1
Background: We conducted a randomized, double blind, placebo controlled study to evaluate the safety and immunogenicity of a bivalent norovirus virus-like particle (VLP) vaccine given by the intramuscular (IM) route. The vaccine included a GI.1 (Norwalk) VLP and a consensus GII.4 norovirus VLP adjuvanted with both Monophosphoryl Lipid A (MPL) (GSK) (0.05mg) and alum (0.5mg) with escalating dosages (5ug, 15ug, 50ug, and 150ug) of each VLP.  

Methods: Twelve healthy adults ages 18-49 years, were enrolled into four sequential dosage groups (total N = 48) and randomized 5:1 to receive two doses of vaccine or saline control 4 weeks apart IM. Safety assessment included solicited local and systemic symptoms for 7 days, unsolicited symptoms for 28 days and Serious Adverse Events for one year. Sera for total ELISA (G,A,M) antibodies and peripheral blood mononuclear cells (PBMCs) for IgG and IgA antibody secreting cells (ASC) via Elispot were obtained prior to and after vaccination.

Results: All four groups have been enrolled and post-dose two data are available from the first 3 dosage groups (30 vaccinees). Pain or tenderness was the most common local symptom reported whereas headache, myalgia, or malaise was the most common systemic symptom. No vaccinees reported fever or related SAEs. Robust anamnestic ELISA antibody responses were observed for both VLP antigens 7 days after the first dose of each dosage group and a second dose did not boost the dose one responses. Likewise, the IgG and IgA Elispot responses were robust 7 days after the first dose of each dosage for both VLP antigens. Notably, the robust ASC responses were biased to IgA vs. IgG and among the B cells with an ASC phenotype (CD27+ CD38++ CD138+), we observed mucosal homing (beta 7) and chemokine (CCR10) receptor phenotype by flow cytometry.

Conclusion: The preliminary data support that this investigational norovirus vaccine was generally well tolerated, highly immunogenic and stimulated both IgG and IgA antibodies. The initial IM dose boosted preexisting antibody levels to high titer in previously primed (seropositive) adults.

Subject Category: I. Adult and Pediatric Vaccines

Sharon Frey, MD1, John J. Treanor, MD2, Robert L. Atmar, MD3, David Topham, PhD2, Wilbur H. Chen, MD4, Jennifer Ferreira, ScM, RAC5, Robert F. Bargatze6, Paul M. Mendelman, MD6 and Charles Richardson, PhD6, (1)Internal Medicine, St Louis University School of Medicine, St Louis, MO, (2)University of Rochester, Rochester, NY, (3)Medicine, Baylor College of Medicine, Houston, TX, (4)Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, (5)EMMES Corporation, Rockville, MD, (6)LigoCyte Pharmaceuticals, Inc., Bozeman, MT


S. Frey, LigoCyte Pharmaceuticals, Inc.: Investigator and Research Contractor, Research support

J. J. Treanor, Protein Sciences Corporation: Investigator, Research support

R. L. Atmar, Ligocyte Pharmaceutical: Investigator, Research support

D. Topham, LigoCyte Pharmaceuticals: Investigator and Research Contractor, Research support

W. H. Chen, LigoCyte : Consultant, Research support
Functional Genetics: Consultant, Consulting fee
Integrated BioTherapeutics: Investigator, Research support

J. Ferreira, The EMMES Corporation: Research Contractor, Research support

R. F. Bargatze, LigoCyte Pharmaceuticals, Inc: Employee and Shareholder, Salary

P. M. Mendelman, LigoCyte Pharmaceuticals Inc.: Employee and Shareholder, Salary and stock options

C. Richardson, LigoCyte pharmaceuticals: Employee and Shareholder, Salary

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.