BACKGROUND: Immune responses to novel pandemic influenza vaccines may be influenced by previous exposure to antigenically similar seasonal strains. METHODS: An open-label, randomized, phase I/II study was conducted to assess the immunogenicity and safety of a non-adjuvanted, inactivated whole-virus H1N1 A/California/07/2009 vaccine. 408 subjects were stratified by age (18-59 and >60 years) and randomized 1:1 to receive two vaccinations with either 3.75 or 7.5 μg hemagglutinin antigen 21 days apart. Safety, immunogenicity and the influence of seasonal influenza vaccination and antibody cross-reactivity with a seasonal H1N1 strain was assessed. RESULTS: A single vaccination with either dose induced substantial increases in H1N1 A/California/07/2009 hemagglutination inhibition (HI) and neutralizing (MN) antibody titers in both adult and elderly subjects. A single 7.5 μg dose induced seroprotection rates of 86.9% in adults and 75.2% in elderly subjects. Two 7.5 μg vaccinations induced seroprotection rates in adult and elderly subjects of 90.9% and 89.1%, respectively. The robust immune response to vaccination was confirmed by analyses of neutralizing antibody titers. Both HI and MN antibodies persisted for ≥ 6 months post-vaccination. Between 34% and 49% of subjects had seroprotective levels of H1N1 A/California/07/2009 antibodies at baseline. Higher baseline HI titers were associated with receipt of the 2008-09 or 2009-10 seasonal influenza vaccine. High baseline A/California/07/2009neutralizing antibody titers were also associated with high baseline titers against A/New Caledonia/20/99, a seasonal H1N1 strain which circulated and was included in the seasonal vaccine from 2000-01 to 2006-07. Pre-adsorption with A/H1N1/New Caledonia/20/99 antigen reduced A/H1N1/California/07/2009 baseline titers in 55% of tested sera. The vaccine was well tolerated with low rates of fever. CONCLUSIONS: A whole-virus H1N1 A/California/07/2009 vaccine was safe and well tolerated and a single dose induced substantial immune responses similar to seasonal influenza vaccines, probably due to immunological priming by previous seasonal influenza vaccines or infections.
RCT Entities:
BACKGROUND: Immune responses to novel pandemic influenza vaccines may be influenced by previous exposure to antigenically similar seasonal strains. METHODS: An open-label, randomized, phase I/II study was conducted to assess the immunogenicity and safety of a non-adjuvanted, inactivated whole-virus H1N1 A/California/07/2009 vaccine. 408 subjects were stratified by age (18-59 and >60 years) and randomized 1:1 to receive two vaccinations with either 3.75 or 7.5 μg hemagglutinin antigen 21 days apart. Safety, immunogenicity and the influence of seasonal influenza vaccination and antibody cross-reactivity with a seasonal H1N1 strain was assessed. RESULTS: A single vaccination with either dose induced substantial increases in H1N1 A/California/07/2009 hemagglutination inhibition (HI) and neutralizing (MN) antibody titers in both adult and elderly subjects. A single 7.5 μg dose induced seroprotection rates of 86.9% in adults and 75.2% in elderly subjects. Two 7.5 μg vaccinations induced seroprotection rates in adult and elderly subjects of 90.9% and 89.1%, respectively. The robust immune response to vaccination was confirmed by analyses of neutralizing antibody titers. Both HI and MN antibodies persisted for ≥ 6 months post-vaccination. Between 34% and 49% of subjects had seroprotective levels of H1N1 A/California/07/2009 antibodies at baseline. Higher baseline HI titers were associated with receipt of the 2008-09 or 2009-10 seasonal influenza vaccine. High baseline A/California/07/2009 neutralizing antibody titers were also associated with high baseline titers against A/New Caledonia/20/99, a seasonal H1N1 strain which circulated and was included in the seasonal vaccine from 2000-01 to 2006-07. Pre-adsorption with A/H1N1/New Caledonia/20/99 antigen reduced A/H1N1/California/07/2009 baseline titers in 55% of tested sera. The vaccine was well tolerated with low rates of fever. CONCLUSIONS: A whole-virus H1N1 A/California/07/2009 vaccine was safe and well tolerated and a single dose induced substantial immune responses similar to seasonal influenza vaccines, probably due to immunological priming by previous seasonal influenza vaccines or infections.
Authors: Gerald Aichinger; Barbara Grohmann-Izay; Maikel V W van der Velden; Sandor Fritsch; Manuela Koska; Daniel Portsmouth; Mary Kate Hart; Wael El-Amin; Otfried Kistner; P Noel Barrett Journal: Clin Vaccine Immunol Date: 2014-10-29
Authors: Walter Wodal; Michael G Schwendinger; Helga Savidis-Dacho; Brian A Crowe; Christine Hohenadl; Richard Fritz; Peter Brühl; Daniel Portsmouth; Anita Karner-Pichl; Dalida Balta; Leopold Grillberger; Otfried Kistner; P Noel Barrett; M Keith Howard Journal: PLoS One Date: 2015-02-26 Impact factor: 3.240
Authors: David Furman; Vladimir Jojic; Brian Kidd; Shai Shen-Orr; Jordan Price; Justin Jarrell; Tiffany Tse; Huang Huang; Peder Lund; Holden T Maecker; Paul J Utz; Cornelia L Dekker; Daphne Koller; Mark M Davis Journal: Mol Syst Biol Date: 2013-04-16 Impact factor: 11.429