Assessment of squalene adjuvanted and non-adjuvanted vaccines against pandemic H1N1 influenza in children 6 months to 17 years of age.

Vaccines were urgently needed in 2009 against A/H1N1 pandemic influenza. Based on the H5N1 experience, it was originally thought that 2 doses of an adjuvanted vaccine were needed for adequate immunogenicity. We tested H1N1 vaccines with or without AF03, a squalene-based adjuvant, in children. Two randomized, open-label, trials were conducted. Participants 3-17 y received two injections of 3.8 mu g or 7.5 mu g hemagglutinin (HA) with adjuvant or 15 mu g HA without adjuvant. Participants aged 6-35 mo received two injections of 1.9 mu g or 3.8 mu g HA with full or half dose adjuvant or 7.5 mu g HA without adjuvant. All subjects 3 to 17 y reached seroprotection (hemagglutination inhibition (HI) titer >= 40) after the first dose of the adjuvanted vaccine, and 94% and 98% in the 3-8 and 9-17 y groups respectively with the non-adjuvanted vaccine. In children aged 6-35 mo responses were modest after one dose, but after two doses virtually all children were seroprotected regardless of HA or adjuvant dose. In this age group, antibody titers were 5 to 7 times higher after adjuvanted than non-adjuvanted vaccine. The higher responses with the adjuvanted vaccine were also reflected as better antibody persistence. There was no clustering of adverse events that would be suggestive of a safety signal. While a single injection was sufficient in subjects from 3 y, in children aged 6-35 mo two injections of this A/H1N1 pandemic influenza vaccine were required. Formulation of this vaccine with adjuvant provided a significant advantage for immunogenicity in the latter age group.