Adjuvanted Intranasal Norwalk Virus-Like Particle Vaccine Elicits Antibodies and Antibody-Secreting Cells That Express Homing Receptors for Mucosal and Peripheral Lymphoid Tissues
12/2010
Journal Article
Authors:
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.
Secondary:
J Infect Dis
Volume:
202
Pagination:
1648-1658
URL:
http://www.ncbi.nlm.nih.gov/pubmed/20979455
Keywords:
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
Abstract:
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.
