A total of 2669 participants aged 10–40 years received one dose of either fully liquid MenACWY-CRM (1337 participants) or licensed MenACWY-CRM (1332 participants), of which 25.6% (overall 683 participants: 342 in MenACWY liquid group; 341 in MenACWY licensed group) were aged 10–17 years. Main demographic characteristics were comparable between vaccine groups for the overall population and for the analysis by age group (Fig. 1).

Demographic characteristics of participants included in the pooled analysis of safety using data from two phase 2b clinical studies in which participants received a single dose of either the fully liquid investigational presentation (MenACWY liquid) or the licensed presentation (MenACWY licensed) of MenACWY-CRM vaccine. aOne participant was aged 44 years at enrolment and was excluded from the per-protocol immunogenicity analysis [12] but was included in the analysis of safety. N = number of participants who received either MenACWY liquid or MenACWY licensed vaccine; SD = standard deviation

Overall, solicited AEs were reported in the 7-day post-vaccination period by similar proportions of participants in each vaccine group (69.2% in MenACWY liquid group; 68.2% in MenACWY licensed group). The proportion of participants reporting solicited local AEs was 46.0% in the MenACWY liquid group and 43.5% in the MenACWY licensed group, with injection site pain being most frequently reported (44.4 and 41.8%, respectively) (Table 1). Solicited systemic AEs were reported by 55.2% of participants in the MenACWY liquid group and 54.1% in the MenACWY licensed group, and the most frequent were headache (36.9 and 35.6%, respectively) and fatigue (36.2%, both groups) (Table 1).

In the age group analyses, any solicited AEs were reported by 72.4% of participants aged 10–17 years in the MenACWY liquid group and 72.1% in the MenACWY licensed group, and by 68.1 and 66.9%, respectively, of participants aged 18–40 years. Within each age group, the proportion of participants reporting each solicited local AE was similar between vaccine groups, with injection site pain most frequently reported (Table 2). Erythema and induration at the injection site tended to be reported more frequently in participants aged 10–17 years than in adults (Table 2).

Solicited systemic AEs were reported by 60.0% of participants aged 10–17 years in the MenACWY liquid group and 57.8% in the MenACWY licensed group, and by 53.5 and 52.9%, respectively, of those aged 18–40 years. The most frequently reported systemic AEs in each age group were headache (10–17 years: 42.9% in MenACWY liquid group and 36.7% in MenACWY licensed group; 18–40 years: 34.8 and 35.3%, respectively) and fatigue (10–17 years: 34.1 and 36.4%, respectively; 18–40 years: 36.9 and 36.2%, respectively) (Table 2). Comparison of the MenACWY liquid group and MenACWY licensed group within each age group showed similar proportions of participants reporting each solicited systemic AE between vaccine groups for both the 10–17 years and 18–40 years age groups. Several of the systemic AEs (chills, fever, and loss of appetite) tended to be reported by a lower proportion of adult participants than adolescents in the MenACWY licensed group (Table 2).

Solicited local and systemic AEs were generally mild to moderate in intensity, with few reports of severe solicited AEs (Tables 1, 2). There were only two reports of fever with temperature ≥ 40 °C, one in the MenACWY liquid group (18–40 years age group) and the other in the MenACWY licensed group (10–17 years age group), occurring within 3 days of vaccination.

Proportions of participants reporting unsolicited AEs within 30 days of vaccination were similar between the two vaccine groups overall and by age group (Table 3). Overall, the three most frequently reported unsolicited AEs in the 29-day post-vaccination period were the same in each vaccine group: headache (3.6% in MenACWY liquid group and 3.8% in MenACWY licensed group), nasopharyngitis (1.8 and 2.3%, respectively), and upper respiratory tract infection (1.9 and 1.4%, respectively). Injection site pain was reported by 1.4 and 1.0%, respectively, injection site erythema by 1.2 and 0.9%, and rhinitis by 0.7 and 1.3%, respectively.

In the 10–17 years age group, injection site pain was reported by 11 participants (3.2%) in the MenACWY liquid group and seven (2.1%) in the MenACWY licensed group, injection site erythema by eight (2.3%) and five (1.5%) participants, respectively, and headache by seven (2.0%) and five (1.5%) participants, respectively. In the 18–40 years age group, injection site pain was reported by eight participants (0.8%) in the MenACWY liquid group and six (0.6%) in the MenACWY licensed group, injection site erythema by eight (0.8%) and seven (0.7%) participants, respectively, and headache by eight (0.8%) and 11 (1.1%) participants, respectively.

At least one unsolicited AE considered related to vaccination was reported in the 29-day post-vaccination period by 6.2% of participants in the MenACWY liquid group and 5.0% in the MenACWY licensed group. In the age group analyses, vaccine-related unsolicited AEs were reported by 7.3% of participants aged 10–17 years in the MenACWY liquid group and 5.0% of the MenACWY licensed group, and by 5.8 and 5.0%, respectively, of those aged 18–40 years. Overall, the three most frequently reported related unsolicited AEs were the same in each vaccine group: injection site pain (1.4% in MenACWY liquid group and 1.0% in MenACWY licensed group), injection site erythema (1.2 and 0.9%, respectively), and headache (1.1 and 1.2%, respectively).

During the entire safety follow-up period of 6 months, unsolicited AEs were reported by 32.2% of participants in the MenACWY liquid group and 31.2% in the MenACWY licensed group overall; by age group, these percentages were 36.3 and 28.4% for the 10–17 years group and 30.8 and 32.2% for the 18–40 years group (Table 3). Medically attended AEs were reported by 18.6 and 17.3% of participants in the MenACWY liquid group and MenACWY licensed group, respectively. Medically attended AEs assessed as related to vaccination were reported by few participants: 14 (1.0%) in the MenACWY liquid group and 11 (0.8%) in the MenACWY licensed group; nine were aged 10–17 years in each vaccine group. In adolescents, the most frequent vaccine-related medically attended AEs were, irrespective of vaccine group, injection site pain, reported by five participants (1.5%) in the MenACWY liquid group and four (1.2%) in the MenACWY licensed group, injection site induration, reported by four (1.2%) and three (0.9%) participants, respectively, and injection site erythema, reported by four (1.2%) and five (1.5%) participants, respectively. In the 18–40 years group, each medically attended AE considered related to vaccination was reported by one participant only (0.1%).

There were no reports of AEs leading to participant withdrawal from the two studies.

Fourteen participants in each group (1.0%, MenACWY liquid group; 1.1%, MenACWY licensed group) reported SAEs in the 6-month safety follow-up study period (Table 3). Fifteen SAEs were reported by 14 participants in the MenACWY liquid group: non-infective appendicitis, dengue fever, tooth abscess, post-procedural hemorrhage, soft tissue injury, tibia fracture, hemiplegic migraine, incomplete spontaneous abortion, spontaneous abortion (two participants), ruptured ovarian cyst, depression, attempted suicide, and (both in a single participant) ruptured ovarian cyst and pleural effusion. There were 14 SAEs reported by 14 participants in the MenACWY licensed group: atrial flutter, phimosis, hyperthyroidism, hernia, biliary colic, dengue fever, otitis externa, jaw fracture, wrist fracture, malignant melanoma, uterine cancer, tension headache, ectopic pregnancy, and adnexa uteri pain. Of the 14 participants in each group reporting SAEs, three were aged 10–17 years in the MenACWY liquid group (SAEs: post-procedural hemorrhage, depression, and ruptured ovarian cyst) and two were aged 10–17 years in the MenACWY licensed group (phimosis and otitis externa).

No SAE was considered to be related to the study vaccines and there were no deaths reported.