Adjuvanted Intranasal Norwalk Virus-Like Particle Vaccine Elicits Antibodies and Antibody-Secreting Cells That Express Homing Receptors for Mucosal and Peripheral Lymphoid Tissues
Year of Publication
El-Kamary, S; Pasetti, M; Mendelman, P; Frey, S; Bernstein, D; Treanor, J; Ferreira, J; Chen, W; Sublett, R; Richardson, C; Bargatze, R; Sztein, M; Tacket, C
J Infect Dis
Adjuvants- Immunologic; Administration- Intranasal; Adolescent; Adult; Antibodies- Viral; Caliciviridae Infections; Chitosan; Double-Blind Method; gastroenteritis; Hemagglutination Inhibition Tests; Lipid A; Lymphoid Tissue; Middle Aged; Mucou
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.