title: Intranasal vaccination with a replication-deficient influenza virus induces heterosubtypic neutralising mucosal IgA antibodies in humans.
abstract: We investigated the cross-neutralising potential of serum and nasal wash samples from volunteers who were intranasally immunised once with a monovalent replication-deficient delNS1-H1N1 influenza virus vaccine (7.7log10TCID50/volunteer). Eight out of twelve (8/12) vaccinees responded to vaccination with a significant increase of antibody levels in serum IgG ELISA, mucosal IgA ELISA, MNA or HAI. Four responders showed delNS1-specific ELISA IgA increases and revealed excellent homosubtypic neutralising activity in serum and mucosal washings (4/4). However, 0/4 of the sera but 3/4 of the nasal washings neutralised also heterosubtypic H3N2 and H5N1 influenza viruses. Depletion experiments proved that IgA but not IgG is responsible for the cross-neutralising activity of the nasal wash sample. Our findings indicate that the induction of virus-neutralising IgA may represent a valuable correlate of cross-protection of intranasal influenza vaccines and that the delNS1 concept constitutes a promising approach to protect humans from seasonal and pandemic influenza threats.
  
  
  BACKGROUND
  NCT00724997.
authors.affiliation: AVIR Green Hills Biotechnology AG, Vienna, Austria; University of Natural Resources and Life Sciences, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Morokutti
authors.affiliation: AVIR Green Hills Biotechnology AG, Vienna, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Muster
authors.affiliation: AVIR Green Hills Biotechnology AG, Vienna, Austria. Electronic address: efbio6@gmail.com.
authors.forename: B
authors.initials: B
authors.lastname: Ferko
mesh_terms: D000281:Administration, Intranasal; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood; D056738:Cross Protection; D004311:Double-Blind Method; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D053118:Influenza A Virus, H1N1 Subtype; D053122:Influenza A Virus, H3N2 Subtype; D053124:Influenza A Virus, H5N1 Subtype; D007252:Influenza Vaccines / Q000627:therapeutic use*; D007251:Influenza, Human / Q000517:prevention & control*; D009500:Neutralization Tests; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated
keywords: Cross-reactive antibodies; Heterologous immunity; Nasal wash IgA; Single intranasal immunisation; delNS1 influenza virus vaccine