Adjuvanted intranasal Norwalk virus-like particle vaccine elicits antibodies and antibody-secreting cells that express homing receptors for mucosal and peripheral lymphoid tissues.

Publication Type
Journal Article
Year of Publication
El-Kamary, Samer S; Pasetti, Marcela F; Mendelman, Paul M; Frey, Sharon E; Bernstein, David I; Treanor, John J; Ferreira, Jennifer; Chen, Wilbur H; Sublett, Richard; Richardson, Charles; Bargatze, Robert F; Sztein, Marcelo B; Tacket, Carol O
J Infect Dis
Date Published
2010 Dec 01
Adjuvants, Immunologic; Administration, Intranasal; Adolescent; Adult; Antibodies, Viral; Antibody-Producing Cells; Caliciviridae Infections; Chitosan; Double-Blind Method; gastroenteritis; Hemagglutination Inhibition Tests; Humans; Lipid A; Lymphoid Tissue; Middle Aged; Mucous Membrane; Norwalk virus; Receptors, Lymphocyte Homing; Viral Vaccines; Young Adult

BACKGROUND: Noroviruses cause significant morbidity and mortality from acute gastroenteritis in all age groups worldwide.

METHODS: We conducted 2 phase 1 double-blind, controlled studies of a virus-like particle (VLP) vaccine derived from norovirus GI.1 genotype adjuvanted with monophosphoryl lipid A (MPL) and the mucoadherent chitosan. Healthy subjects 18-49 years of age were randomized to 2 doses of intranasal Norwalk VLP vaccine or controls 21 days apart. Study 1 evaluated 5-, 15-, and 50-μg dosages of Norwalk antigen, and study 2 evaluated 50- and 100-μg dosages. Volunteers recorded symptoms for 7 days after dosing, and safety was followed up for 180 days. Blood samples were collected for serological profile, antibody secreting cells (ASCs), and analysis of ASC homing receptors.

RESULTS: The most common symptoms were nasal stuffiness, discharge, and sneezing. No vaccine-related serious adverse events occurred. Norwalk VLP-specific immunoglobulin G and immunoglobulin A antibodies increased 4.8- and 9.1-fold, respectively, for the 100-μg dosage level. All subjects tested who received the 50- or 100-μg vaccine dose developed immunoglobulin A ASCs. These cells expressed molecules associated with homing to mucosal and peripheral lymphoid tissues.

CONCLUSIONS: The intranasal monovalent adjuvanted Norwalk VLP vaccine was well tolerated and highly immunogenic and is a candidate for additional study.