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Randomized clinical trial of immunogenicity and safety of a recombinant H1N1/2009 pandemic influenza vaccine containing Advax? polysaccharide adjuvant ☆
David L. Gordona, E-mail the corresponding author,
Dimitar Sajkovb, E-mail the corresponding author,
Richard J. Woodmand, E-mail the corresponding author,
Yoshikazu Honda-Okubof, E-mail the corresponding author,
Manon M.J. Coxe, E-mail the corresponding author,
Susanne Heinzelf, E-mail the corresponding author,
Nikolai Petrovskyb, c, f, Corresponding author contact information, E-mail the corresponding author
a Department of Microbiology and Infectious Diseases, Flinders Medical Centre and Flinders University, Adelaide 5042, Australia
b Australian Respiratory and Sleep Medicine Institute, Flinders Medical Centre and Flinders University, Adelaide 5042, Australia
c Department of Endocrinology, Flinders Medical Centre and Flinders University, Adelaide 5042, Australia
d Discipline of General Practice, Flinders University, Australia
e Protein Sciences Corporation, Meriden, CT, USA
f Vaxine Pty Ltd, Flinders Medical Centre, Adelaide, SA 5042, Australia
Received 17 January 2012. Revised 25 May 2012. Accepted 5 June 2012. Available online 17 June 2012.
http://dx.doi.org/10.1016/j.vaccine.2012.06.009,
Abstract
Background
Timely vaccine supply is critical during influenza pandemics. A recombinant hemagglutinin (rHA)-based vaccine could overcome production hurdles of egg-based vaccines but has never previously been tested in a real-life pandemic setting. The primary aim was to determine the efficacy of a recombinant pandemic vaccine and whether its immunogenicity could be enhanced by a novel polysaccharide adjuvant (Advax?).
Methods
281 adults aged 18?70 years were recruited in a randomized, subject and observer blinded, parallel-group study of rHA H1N1/2009 vaccine with or without adjuvant. Immunizations were at 0 and 3 weeks with rHA 3, 11 or 45 μg. Serology and safety was followed for 6 months.
Results
At baseline, only 9.1% of subjects (95% CI: 6.0?13.2) had seroprotective H1N1/2009 titers. Seroconversion rates varied by rHA dose, presence of adjuvant, subject age and number of immunizations. Eighty percent (95% CI: 52?96) of 18?49 year olds who received rHA 45 μg with adjuvant were seroprotected at week 3, representing a 11.1-fold increase in antibody titers from baseline. Advax? adjuvant increased seroprotection rates by 1.9 times after the first, and 2.5 times after the second, immunization when compared to rHA alone. Seroprotection was sustained at 26 weeks and the vaccine was well tolerated with no safety issues.
Conclusions
The study confirmed the ability to design, manufacture, and release a recombinant vaccine within a short time from the start of an actual influenza pandemic. Advax? adjuvant significantly enhanced rHA immunogenicity.
Highlights
► Randomized clinical trial of a novel adjuvanted H1N1/2009 pandemic influenza vaccine. ► Reports first pandemic use of a vaccine based on recombinant hemagglutinin. ► The recombinant vaccine was produced within 12 weeks of the pandemic. ► Advax?, a novel polysaccharide adjuvant, significantly improved vaccine responses.
http://www.sciencedirect.com/science/article/pii/S0264410X12008481
David L. Gordona, E-mail the corresponding author,
Dimitar Sajkovb, E-mail the corresponding author,
Richard J. Woodmand, E-mail the corresponding author,
Yoshikazu Honda-Okubof, E-mail the corresponding author,
Manon M.J. Coxe, E-mail the corresponding author,
Susanne Heinzelf, E-mail the corresponding author,
Nikolai Petrovskyb, c, f, Corresponding author contact information, E-mail the corresponding author
a Department of Microbiology and Infectious Diseases, Flinders Medical Centre and Flinders University, Adelaide 5042, Australia
b Australian Respiratory and Sleep Medicine Institute, Flinders Medical Centre and Flinders University, Adelaide 5042, Australia
c Department of Endocrinology, Flinders Medical Centre and Flinders University, Adelaide 5042, Australia
d Discipline of General Practice, Flinders University, Australia
e Protein Sciences Corporation, Meriden, CT, USA
f Vaxine Pty Ltd, Flinders Medical Centre, Adelaide, SA 5042, Australia
Received 17 January 2012. Revised 25 May 2012. Accepted 5 June 2012. Available online 17 June 2012.
http://dx.doi.org/10.1016/j.vaccine.2012.06.009,
Abstract
Background
Timely vaccine supply is critical during influenza pandemics. A recombinant hemagglutinin (rHA)-based vaccine could overcome production hurdles of egg-based vaccines but has never previously been tested in a real-life pandemic setting. The primary aim was to determine the efficacy of a recombinant pandemic vaccine and whether its immunogenicity could be enhanced by a novel polysaccharide adjuvant (Advax?).
Methods
281 adults aged 18?70 years were recruited in a randomized, subject and observer blinded, parallel-group study of rHA H1N1/2009 vaccine with or without adjuvant. Immunizations were at 0 and 3 weeks with rHA 3, 11 or 45 μg. Serology and safety was followed for 6 months.
Results
At baseline, only 9.1% of subjects (95% CI: 6.0?13.2) had seroprotective H1N1/2009 titers. Seroconversion rates varied by rHA dose, presence of adjuvant, subject age and number of immunizations. Eighty percent (95% CI: 52?96) of 18?49 year olds who received rHA 45 μg with adjuvant were seroprotected at week 3, representing a 11.1-fold increase in antibody titers from baseline. Advax? adjuvant increased seroprotection rates by 1.9 times after the first, and 2.5 times after the second, immunization when compared to rHA alone. Seroprotection was sustained at 26 weeks and the vaccine was well tolerated with no safety issues.
Conclusions
The study confirmed the ability to design, manufacture, and release a recombinant vaccine within a short time from the start of an actual influenza pandemic. Advax? adjuvant significantly enhanced rHA immunogenicity.
Highlights
► Randomized clinical trial of a novel adjuvanted H1N1/2009 pandemic influenza vaccine. ► Reports first pandemic use of a vaccine based on recombinant hemagglutinin. ► The recombinant vaccine was produced within 12 weeks of the pandemic. ► Advax?, a novel polysaccharide adjuvant, significantly improved vaccine responses.
http://www.sciencedirect.com/science/article/pii/S0264410X12008481