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.
Bibliographical noteFunding Information:
This study was supported by the EU FP7 Univax (601738), FP6 PANFLUVAC and the EU FP7 NASPANVAC and RCN Globvac (220670) projects as well as intramurally by the Influenza Centre, University of Bergen. We thank the Ministry of Health and Care Services, Norway, Ole Hovli for help with the SPR instrument, Helena Danielsson, Uppsala, Sweden for advice with SPR analysis, Crucell, The Netherlands for providing the vaccine, ISCONOVA, Uppsala, Sweden for providing the Matrix M™ adjuvant and the staff at the Influenza Centre, Bergen for help with performing experiments.
- Antibody avidity
- Influenza H5N1
- Matrix M™
- Pandemic influenza
- Virosomal vaccine
- Virus neutralization