Randomized, multicenter trial of a single dose of AS03-adjuvanted or unadjuvanted H1N1 2009 pandemic influenza vaccine in children 6 months to <9 years of age: safety and immunogenicity.
BACKGROUND
During the 2009-2010 influenza pandemic, we evaluated the immunogenicity and safety of different H1N1 2009 pandemic influenza vaccines delivering various viral hemagglutinin (HA) doses with or without AS03 (a tocopherol oil-in-water emulsion-based adjuvant system) in children (NCT00976820).


METHODS
Three hundred twenty-two healthy children 6 months to <9 years of age were randomized to receive 2 doses of nonadjuvanted (15 µg or 7.5 µg HA) or adjuvanted vaccine (3.75 µg HA/AS03A or 1.9 µg HA/AS03B), 21 days apart. Blood samples before and after each dose were tested for immune responses using hemagglutination inhibition and microneutralization assays. Safety assessments were done up to day 385.


RESULTS
The first dose of both AS03-adjuvanted vaccines elicited strong immune responses (seroprotection rates: 98.3%/99.0%; seroconversion rates: 94.9%/97.0%; geometric mean fold rises: 36.2/33.6), which were higher post-dose 2 (seroprotection rate: 100.0%/100%; seroconversion rate: 100.0%/98.8%; geometric mean fold rise: 157.1/151.6), meeting European regulatory criteria on days 21 and 42. The nonadjuvanted 15 µg HA vaccine also met the regulatory criteria after each dose; the 7.5 µg HA vaccine met them only post-dose 2. Six months post-dose 1, all vaccines except the nonadjuvanted 7.5 µg HA vaccine met European regulatory criteria. Neutralizing antibody response paralleled the hemagglutination inhibition immune response after each dose. Pain at the injection site, lasting 2-3 days, was more common following adjuvanted than nonadjuvanted vaccination.


CONCLUSIONS
AS03-adjuvanted H1N1 2009 pandemic influenza vaccine (3.75 µg or 1.9 µg HA), administered as 2 doses, was highly immunogenic, induced long-term immune response to 6 months, with a clinically acceptable safety profile in children aged 6 months to <9 years of age.
Canadian Center for Vaccinology and the Departments of Pediatrics and Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada. jmlangle@dal.ca
Joanne M
JM
Langley
Dennis
D
Reich
Naresh
N
Aggarwal
David
D
Connor
Marc H
MH
Lebel
Anil
A
Gupta
Hartley
H
Garfield
Ping
P
Li
Anu
A
Madan
David W
DW
Vaughn
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004338:Drug Combinations; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D009500:Neutralization Tests; D058873:Pandemics / Q000517:prevention & control*; D011136:Polysorbates / Q000008:administration & dosage* / Q000009:adverse effects; D013185:Squalene / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D024505:Tocopherols / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D014611:Vaccination / Q000706:statistics & numerical data; D024502:alpha-Tocopherol / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D004338:Drug Combinations; D007252:Influenza Vaccines; D011136:Polysorbates; D013185:Squalene; C550253:AS03 adjuvant; D024502:alpha-Tocopherol; D024505:Tocopherols