Enhanced immunogenicity of seasonal influenza vaccines in young children using MF59 adjuvant.
BACKGROUND
Children have high morbidity and hospitalization rates from seasonal influenza. Meta-analyses suggest that conventional inactivated influenza vaccines are of low efficacy in young children, making vaccines that induce greater and broader immune protection in this vulnerable population a medical priority. Adjuvanted influenza vaccines may offer a solution.


METHODS
Unprimed healthy children (6 to <36 months) were enrolled in an observer-blinded study and randomly assigned to receive 2 doses of MF59-adjuvanted vaccine (Sub/MF59, n = 130) or nonadjuvanted split vaccine (split, n = 139); subgroups of these (n = 43 and 46, respectively) received a booster dose 1 year later. Safety and clinical tolerability were assessed after each dose. Hemagglutination inhibition antibody titers were measured against influenza A and B strains included in the formulation of the vaccines and against mismatched strains.


RESULTS
Clinical tolerability and safety were generally comparable between vaccine groups, though some transient, mild solicited reactions were more frequent in the Sub/MF59 group. Postvaccination hemagglutination inhibition antibody titers to all 3 vaccine strains were significantly higher with Sub/MF59 than with split vaccine (all comparisons P < 0.001) after each of the 3 vaccine doses. In addition, Sub/MF59 induced significantly higher cross-reactivity against A/H3N2 and A/H1N1 mismatched strains.


CONCLUSIONS
MF59-adjuvanted influenza vaccine was well tolerated in healthy young children after each of 3 doses and induced greater, longer-lasting, and broader immune responses than a nonadjuvanted split vaccine. The enhanced immunogenicity of the adjuvanted vaccine was most evident in very young children and for the B vaccine strain.
Vesikari
Timo
T
Vaccine Research Center, University of Tampere Medical School, Tampere, Finland. Timo.Vesikari@uta.fi
Pellegrini
Michele
M
Karvonen
Aino
A
Groth
Nicola
N
Borkowski
Astrid
A
O'Hagan
Derek T
DT
Podda
Audino
A
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000914:Antibodies, Viral / Q000097:blood; D002675:Child, Preschool; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007223:Infant; D009980:Influenza A virus / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D011136:Polysorbates / Q000008:administration & dosage* / Q000009:adverse effects; D013185:Squalene / Q000008:administration & dosage* / Q000009:adverse effects; D014611:Vaccination / Q000379:methods
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D013185:Squalene