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Adjuvanted Intranasal Norwalk Virus-Like Particle Vaccine Elicits Antibodies and Antibody-Secreting Cells That Express Homing Receptors for Mucosal and Peripheral Lymphoid Tissues


Journal Article

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.

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