title: Serum IgG titres, but not avidity, correlates with neutralizing antibody response after H5N1 vaccination.
abstract: BACKGROUND
  Influenza H5N1 virus constitutes a pandemic threat and development of effective H5N1 vaccines is a global priority. Anti-influenza antibodies directed towards the haemagglutinin (HA) define a correlate of protection. Both antibody concentration and avidity may be important for virus neutralization and resolving influenza disease.
  
  
  METHODS
  We conducted a phase I clinical trial of a virosomal H5N1 vaccine adjuvanted with the immunostimulating complex Matrix M™. Sixty adults were intramuscularly immunized with two vaccine doses (21 days apart) of 30 μg HA alone or 1.5, 7.5 or 30 μg HA adjuvanted with Matrix M™. Serum H5 HA1-specific antibodies and virus neutralization were determined at days 0, 21, 42, 180 and 360 and long-term memory B cells at day 360 post-vaccination. The binding of the HA specific antibodies was measured by avidity NaSCN-elution ELISA and surface plasmon resonance (SPR).
  
  
  RESULTS
  The H5 HA1-specific IgG response peaked after the second dose (day 42), was dominated by IgG1 and IgG3 and was highest in the adjuvanted vaccine groups. IgG titres correlated significantly with virus neutralization at all time points (Spearman r≥0.66, p<0.0001). By elution ELISA, serum antibody avidity was highest at days 180 and 360 post vaccination and did not correlate with virus neutralization. Long-lasting H5 HA1-specific memory B cells produced high IgG antibody avidity similar to serum IgG.
  
  
  CONCLUSIONS
  Maturation of serum antibody avidity continued up to day 360 after influenza H5N1 vaccination. Virus neutralization correlated with serum H5 HA1-specific IgG antibody concentrations and not antibody avidity.
authors.affiliation: Influenza Centre, Department of Clinical Science, University of Bergen, Norway.
authors.forename: Gabriel Kristian
authors.initials: GK
authors.lastname: Pedersen
authors.affiliation: Respiratory Unit, Public Health England (PHE) Colindale, London, UK.
authors.forename: Katja
authors.initials: K
authors.lastname: Höschler
authors.affiliation: Influenza Centre, Department of Clinical Science, University of Bergen, Norway.
authors.forename: Sara Marie
authors.initials: SM
authors.lastname: Øie Solbak
authors.affiliation: Influenza Centre, Department of Clinical Science, University of Bergen, Norway.
authors.forename: Geir
authors.initials: G
authors.lastname: Bredholt
authors.affiliation: Influenza Centre, Department of Clinical Science, University of Bergen, Norway.
authors.forename: Rishi Delan
authors.initials: RD
authors.lastname: Pathirana
authors.affiliation: Respiratory Unit, Public Health England (PHE) Colindale, London, UK.
authors.forename: Aram
authors.initials: A
authors.lastname: Afsar
authors.affiliation: Respiratory Unit, Public Health England (PHE) Colindale, London, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Breakwell
authors.affiliation: Influenza Centre, Department of Clinical Science, University of Bergen, Norway.
authors.forename: Jane Kristin
authors.initials: JK
authors.lastname: Nøstbakken
authors.affiliation: Department of Molecular Biology, University of Bergen, Norway.
authors.forename: Arnt Johan
authors.initials: AJ
authors.lastname: Raae
authors.affiliation: Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Norway.
authors.forename: Karl Albert
authors.initials: KA
authors.lastname: Brokstad
authors.affiliation: Influenza Centre, Department of Clinical Science, University of Bergen, Norway; Section for Infectious Diseases, Medical Department, Haukeland University Hospital, N-5021 Bergen, Norway.
authors.forename: Haakon
authors.initials: H
authors.lastname: Sjursen
authors.affiliation: Respiratory Unit, Public Health England (PHE) Colindale, London, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Zambon
authors.affiliation: Influenza Centre, Department of Clinical Science, University of Bergen, Norway; Jebsen Centre for Influenza Vaccine Research, University of Bergen, Norway; Department of Research and Development, Haukeland University Hospital, Bergen, Norway. Electronic address: rebecca.cox@k2.uib.no.
authors.forename: Rebecca Jane
authors.initials: RJ
authors.lastname: Cox
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D000915:Antibody Affinity; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007273:Injections, Intramuscular; D008875:Middle Aged; D009500:Neutralization Tests; D044967:Serum / Q000276:immunology; D020349:Surface Plasmon Resonance; D014611:Vaccination / Q000379:methods*; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007252:Influenza Vaccines
keywords: Antibody avidity; ISCOM; Influenza H5N1; Matrix M™; Pandemic influenza; Virosomal vaccine; Virus neutralization