tetano
Editor, Senior Moderator
Pre-vaccination immunity and immune responses to a cell culture-derived whole-virus H1N1 vaccine are similar to a seasonal influenza vaccine ☆
Hartmut J. Ehrlicha, Corresponding author contact information, E-mail the corresponding author,
Markus M?llerb,
Herwig Kollaritschc,
Fritz Pinld,
Bernhard Schmitte,
Markus Zeitlingerb,
Alexandra Loew-Basellif,
Thomas R. Kreilg,
Otfried Kistnerg,
Daniel Portsmouthg,
Sandor Fritscha,
Friedrich Maritscha,
Gerald Aichingerf,
Borislava G. Pavlovaa,
P. Noel Barrettg
a Global R&D, Baxter BioScience, Vienna, Austria
b Department of Clinical Pharmacology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
c Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria
d Sanatorium Leech, Graz, Austria
e Group Practice for Internal Medicine Dr. Regner & Dr. Schmitt, Mainz, Germany
f Vaccine R&D, Baxter BioScience, Vienna, Austria
g Vaccine R&D, Baxter BioScience, Orth/Donau, Austria
Received 12 December 2011. Revised 22 February 2012. Accepted 20 March 2012. Available online 1 April 2012.
http://dx.doi.org/10.1016/j.vaccine.2012.03.061, How to Cite or Link Using DOI
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.
Highlights
► Vero cell-derived whole-virus H1N1 vaccine is safe and immunogenic in young and older adults. ► All EU immunological licensing thresholds met in both populations by a single 7.5 μg dose. ► Vaccine-induced HI antibodies persisted for ≥6 months post-vaccination. ► Higher baseline seroprotection rates associated with 2008?09 or 2009?10 seasonal influenza vaccination. ► High baseline titers were probably associated with exposure to H1N1 circulating from 2000 to 2007.
http://www.sciencedirect.com/science/article/pii/S0264410X12004537
Hartmut J. Ehrlicha, Corresponding author contact information, E-mail the corresponding author,
Markus M?llerb,
Herwig Kollaritschc,
Fritz Pinld,
Bernhard Schmitte,
Markus Zeitlingerb,
Alexandra Loew-Basellif,
Thomas R. Kreilg,
Otfried Kistnerg,
Daniel Portsmouthg,
Sandor Fritscha,
Friedrich Maritscha,
Gerald Aichingerf,
Borislava G. Pavlovaa,
P. Noel Barrettg
a Global R&D, Baxter BioScience, Vienna, Austria
b Department of Clinical Pharmacology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
c Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria
d Sanatorium Leech, Graz, Austria
e Group Practice for Internal Medicine Dr. Regner & Dr. Schmitt, Mainz, Germany
f Vaccine R&D, Baxter BioScience, Vienna, Austria
g Vaccine R&D, Baxter BioScience, Orth/Donau, Austria
Received 12 December 2011. Revised 22 February 2012. Accepted 20 March 2012. Available online 1 April 2012.
http://dx.doi.org/10.1016/j.vaccine.2012.03.061, How to Cite or Link Using DOI
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.
Highlights
► Vero cell-derived whole-virus H1N1 vaccine is safe and immunogenic in young and older adults. ► All EU immunological licensing thresholds met in both populations by a single 7.5 μg dose. ► Vaccine-induced HI antibodies persisted for ≥6 months post-vaccination. ► Higher baseline seroprotection rates associated with 2008?09 or 2009?10 seasonal influenza vaccination. ► High baseline titers were probably associated with exposure to H1N1 circulating from 2000 to 2007.
http://www.sciencedirect.com/science/article/pii/S0264410X12004537