title: Recombinant Norwalk virus-like particles given orally to volunteers: phase I study.
abstract: OBJECTIVE
  Norwalk virus (NV) is a major cause of epidemic gastroenteritis. The NV capsid is composed of a single protein that forms recombinant (rNV) virus-like particles (VLPs). In mice, these VLPs are immunogenic when administered orally without adjuvant, and they elicit serum immunoglobulin (Ig) G and intestinal IgA responses. The aim of this study was to evaluate the safety and immunogenicity of rNV VLPs in healthy volunteers.
  
  
  METHODS
  Twenty antibody-positive adults were orally administered rNV VLPs in sterile Milli-Q water on days 1 and 21. Vaccine safety and serum rNV-specific total and subclass IgG and IgA antibody responses were monitored. The immune response induced by the VLPs was compared with the response elicited by replicating virus.
  
  
  RESULTS
  No side effects were observed or reported by the volunteers. Serum IgG responses to rNV VLPs were dose-dependent, and all vaccinees given 250 microgram of rNV VLPs responded with >/=4-fold increases in serum IgG titers. Most of the volunteers (83%; 15 of 18) responded after the first rNV VLP dose and showed no increase in serum IgG titer after the second dose.
  
  
  CONCLUSIONS
  Orally administered rNV VLPs are safe and immunogenic in healthy adults when administered without adjuvant and are useful to test the mucosal delivery of immunogens.
authors.affiliation: Division of Molecular Virology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Ball
authors.forename: D Y
authors.initials: DY
authors.lastname: Graham
authors.forename: A R
authors.initials: AR
authors.lastname: Opekun
authors.forename: M A
authors.initials: MA
authors.lastname: Gilger
authors.forename: R A
authors.initials: RA
authors.lastname: Guerrero
authors.forename: M K
authors.initials: MK
authors.lastname: Estes
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation / Q000502:physiology; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009663:Norwalk virus / Q000276:immunology*; D011995:Recombination, Genetic; D014771:Virion / Q000276:immunology*; D014779:Virus Replication / Q000502:physiology
chemical_list: D000906:Antibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G