In addition, the more stringent Center for Biologics Evaluation and Research (CBER) criteria [lower limits of 95% CI for SPR ≥70% and SCR ≥40%] [26] were met for all study vaccines at Day 21. Six months after the first vaccine dose and prior to the booster dose, the CHMP criteria were still met for all study vaccines, with the highest HI antibody SPRs and GMTs in subjects who received two primary doses of the AS03B-adjuvanted 1.9 μg HA H1N1/2009 vaccine. At this time point,

the CBER criteria were not met for the single dose regimen of the 1.9 μg HA AS03B-adjuvanted HA H1N1/2009 vaccine but were met for all other formulations. The HI antibody SPRs observed following one dose of the AS03-adjuvanted H1N1/2009 vaccines in the current study (98.5–100.0%) are consistent with previously observed SPRs (96.7–100.0%) for similar vaccines in children between high throughput screening assay 6 months and 17 years old [21], [22] and [27]. The observations in the current study are consistent with published literature that one dose of non-adjuvanted H1N1/2009 vaccines can elicit putatively protective levels of HI antibodies in adolescents 10 to 17 years old, 21 days after vaccination [22], [28], [29], [30], [31] and [32], although two doses may be required in younger children [29], [30], [31], [32] and [33].

Previous studies have reported that two doses of AS03B-adjuvanted 1.9 μg HA or 3.75 μg HA H1N1/2009 vaccines induced persistence of HI antibody responses (SPR: >98.0%; SCR: >89.0%) in children through 6 months after vaccination [22] and [23]. In one Venetoclax in vivo of these studies [22], enrolling healthy children

from 6 months to 9 years of age, the parallel study arm with non-adjuvanted 15 μg HA H1N1/2009 vaccine (but not 7.5 μg HA) also elicited long-term persistence of HI antibody response (SPR: 91.5%; SCR: 74.5%), although the HI antibody GMTs (122.7) were lower than that observed for the AS03-adjuvanted vaccines (267.9–296.2). Nassim et al. reported from a dose-ranging study that only the MF59-adjuvanted vaccines with 3.75–15 μg HA antigen doses, but not the non-adjuvanted vaccines with 7.5–30 μg HA antigen doses, met the regulatory criteria through one year after vaccination mafosfamide [34]. This is the first study to assess the concept of priming for immunological memory with AS03-adjuvanted H1N1/2009 vaccines in children 10–17 years old. A rapid increase in HI antibody titers after the booster dose administered at month 6 was observed for all study vaccines, suggesting effective priming irrespective of the one- or two-dose priming regimens. The HI antibody SPRs 7 days after the booster dose were comparable across the treatment groups (97.2–100.0%), although the HI antibody GMTs were higher for the AS03-adjuvanted vaccines (416.7–589.4) compared with those for the non-adjuvanted vaccine (273.4).