title: Adjuvanted intranasal Norwalk virus-like particle vaccine elicits antibodies and antibody-secreting cells that express homing receptors for mucosal and peripheral lymphoid tissues.
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.
authors.affiliation: Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. selkamar@epi.umaryland.edu
authors.forename: Samer S
authors.initials: SS
authors.lastname: El-Kamary
authors.forename: Marcela F
authors.initials: MF
authors.lastname: Pasetti
authors.forename: Paul M
authors.initials: PM
authors.lastname: Mendelman
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Frey
authors.forename: David I
authors.initials: DI
authors.lastname: Bernstein
authors.forename: John J
authors.initials: JJ
authors.lastname: Treanor
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ferreira
authors.forename: Wilbur H
authors.initials: WH
authors.lastname: Chen
authors.forename: Richard
authors.initials: R
authors.lastname: Sublett
authors.forename: Charles
authors.initials: C
authors.lastname: Richardson
authors.forename: Robert F
authors.initials: RF
authors.lastname: Bargatze
authors.forename: Marcelo B
authors.initials: MB
authors.lastname: Sztein
authors.forename: Carol O
authors.initials: CO
authors.lastname: Tacket
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood; D000921:Antibody-Producing Cells / Q000276:immunology / Q000378:metabolism; D017250:Caliciviridae Infections / Q000517:prevention & control* / Q000821:virology; D048271:Chitosan / Q000008:administration & dosage / Q000276:immunology; D004311:Double-Blind Method; D005759:Gastroenteritis / Q000517:prevention & control* / Q000821:virology; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000276:immunology; D008221:Lymphoid Tissue / Q000378:metabolism / Q000821:virology; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000821:virology; D009663:Norwalk virus / Q000276:immunology*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000592:standards; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D008050:Lipid A; D016201:Receptors, Lymphocyte Homing; D014765:Viral Vaccines; D048271:Chitosan; C048436:monophosphoryl lipid A