Randomized clinical trial of immunogenicity and safety of a recombinant H1N1/2009 pandemic influenza vaccine containing Advax™ polysaccharide adjuvant.
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.
Department of Microbiology and Infectious Diseases, Flinders Medical Centre and Flinders University, Adelaide 5042, Australia.
David L
DL
Gordon
Dimitar
D
Sajkov
Richard J
RJ
Woodman
Yoshikazu
Y
Honda-Okubo
Manon M J
MM
Cox
Susanne
S
Heinzel
Nikolai
N
Petrovsky
D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D005260:Female; D006388:Hemagglutinins; D006801:Humans; D007114:Immunization; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D007444:Inulin / Q000031:analogs & derivatives*; D008297:Male; D008875:Middle Aged; D058873:Pandemics; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000009:adverse effects; D014614:Vaccines, Synthetic; D055815:Young Adult
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D006388:Hemagglutinins; D007252:Influenza Vaccines; D011135:Polysaccharides, Bacterial; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; C576871:delta inulin; D007444:Inulin