title: Mucosal Antibodies Induced by Intranasal but Not Intramuscular Immunization Block Norovirus GII.4 Virus-Like Particle Receptor Binding.
abstract: Noroviruses (NoVs) account for the majority of diagnosed cases of viral acute gastroenteritis worldwide. Virus-like particle (VLP)-based vaccines against NoV are currently under development. Serum antibodies that block the binding of NoV VLPs to histo-blood group antigens, the putative receptors for NoV, correlate with protection against NoV infection. The role of functional mucosal antibodies in protection is largely unknown, even though the intestinal mucosa is the entry port for NoV. Balb/c mice were immunized intramuscularly (IM) or intranasally (IN) with NoV GII.4 VLPs, and systemic and mucosal blocking antibody responses were studied. IN immunization elicited NoV-specific serum and mucosal IgG and IgA antibodies, whereas IM immunized animals completely lacked IgA. Both immunization routes induced similar blocking activity in serum but only IN route generated blocking antibodies in mucosa. The level of IgA in the mucosal (nasal) lavages strongly correlated (r = 0.841) with the blocking activity, suggesting that IgA, but not IgG, is the major NoV blocking antibody on mucosal surfaces. The results indicate that only mucosal immunization route induces the development of functional anti-NoV IgA on mucosal surface.
authors.affiliation: Vaccine Research Center, School of Medicine, University of Tampere , Tampere, Finland .
authors.forename: Kirsi
authors.initials: K
authors.lastname: Tamminen
authors.affiliation: Vaccine Research Center, School of Medicine, University of Tampere , Tampere, Finland .
authors.forename: Maria
authors.initials: M
authors.lastname: Malm
authors.affiliation: Vaccine Research Center, School of Medicine, University of Tampere , Tampere, Finland .
authors.forename: Timo
authors.initials: T
authors.lastname: Vesikari
authors.affiliation: Vaccine Research Center, School of Medicine, University of Tampere , Tampere, Finland .
authors.forename: Vesna
authors.initials: V
authors.lastname: Blazevic
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis; D000914:Antibodies, Viral / Q000096:biosynthesis*; D001789:Blood Group Antigens / Q000235:genetics / Q000276:immunology; D017250:Caliciviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D005260:Female; D005759:Gastroenteritis / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D018928:Immunity, Mucosal / Q000187:drug effects; D007115:Immunization Schedule; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007273:Injections, Intramuscular; D007413:Intestinal Mucosa / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D029322:Norovirus / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D011991:Receptors, Virus / Q000235:genetics / Q000276:immunology; D014611:Vaccination; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage* / Q000096:biosynthesis; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000096:biosynthesis
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D001789:Blood Group Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011991:Receptors, Virus; D058425:Vaccines, Virus-Like Particle; D014765:Viral Vaccines