Data were assessed for safety from 701 subjects in the study group aged 3 years or older and 687 subjects in the study group aged 6–35 months. Within the group aged 3 years or older, the paediatric and adolescent population (aged 3–19 years) comprised 246 individuals, and the elderly population (aged 65 years or older) comprised 36 individuals. Demographic characteristics are summarised in Table 1. All participants were ethnically Korean except for one participant in the group aged 6–35 months. There were no women who became pregnant within 21 days after vaccination with IIV4. The two paediatric groups could not be combined because the data were collected over different time periods. Non-influenza vaccination history of the study groups as well as heights and weights of the participants are summarised in Supplementary Table 2.

In the group aged 3 years or older, concomitant medication was received by 304 individuals (43.37%) and among these, the most commonly used class was systemic anti-infectives (46.71%) (Supplementary Table 3). Concomitant vaccination was received by 37 subjects (5.28%) (Supplementary Table 4). In the group aged 6–35 months, 203/687 (29.55%) subjects received concomitant medication, of which the most common category was respiratory system (156/203 subjects, 76.85%) (Supplementary Table 5). Concomitant vaccination was received by 165/687 (24.02%) subjects (Supplementary Table 6).

Among the 701 subjects in the safety population, 98 subjects (13.98%) reported a total of 140 AEs during the 6 year surveillance period (Table 2 and Supplementary Table 7). The most common SOC AE categories were infections and infestations [6.42% (45/701) subjects, 55 events] followed by general disorders and administration site conditions [4.56% (32/701) subjects, 33 events] (Table 2). The most common AE by preferred term was nasopharyngitis [2.43% (17/701) subjects, 17 events]. The list of all AEs within SOC is presented in Supplementary Table 7.

Of the AEs, 42 were ARVs for which a causal relationship with IIV4 could not be ruled out by the investigators, reported by 34 subjects (4.85%) (Table 2). The most common ARV SOC was general disorders and administration site conditions [3.99% (28/701) subjects, 29 events] (Table 2). The most common ARVs by preferred term were administration site pain and administration site swelling, each of which was reported in 1.28% subjects (9/701 subjects, 9 events). The list of all ARVs within SOC is presented in Supplementary Table 7.

Of the AEs, 85 (reported by 62 subjects, 8.84%) were classed as unexpected according to the PI. The most common SOC categories for unexpected AEs were infections and infestations [5.85% (41/701) subjects, 50 events] followed by respiratory, thoracic and mediastinal disorders [1.85% (13/701) subjects, 16 events] and gastrointestinal disorders [1.00% (7/701) subjects, 7 events] (Supplementary Table 8). Seven unexpected ARVs were reported by five subjects (0.71%), which were cough (three events), rhinorrhoea (two events), nasopharyngitis (one event) and pharyngitis (one event) (Supplementary Table 8).

One subject reported a SAE, gastroenteritis. This was not considered a SARV.

About 96.43% of the reported AEs (135/140 events) were considered resolved during the follow-up period. Four AEs with the event terms hyperlipidaemia, pyrexia, rhinorrhoea and pharyngotonsillitis were not resolved during the course of the study, but none were considered to be ARVs. One AE, classed as positional vertigo, was considered resolving and was also not regarded as an ARV. There were no fatal events. All the ARVs were resolved, and the majority (24/42 ARVs, 57.14%) were administration site reactions expected according to the PI [administration site pain and administration site swelling (each 9/42 events, 21.4%), administration site erythema and administration site pruritus (each 3/42 events, 7.1%)].

Of the 140 AEs reported, no medical attention was required for 74 (52.86%) events, and 63 (45.00%) events led to a visit to or from medical personnel (medical doctor). Two (1.43%) events required hospitalisation and one (0.71%) subject went to the emergency room; these events were not ARVs and all resolved during the surveillance period. Most of the reported AEs were mild (115/140, 82.14%), with 24/140 AEs (17.14%) graded as moderate and one event (0.71%) graded as severe. The severe event was a case of influenza.

In the paediatric and adolescent population (aged 3 to < 19 years), 72 AEs were reported by 48 subjects (19.51%), and in the elderly population (aged 65 years or older), four AEs were reported by four subjects (11.11%).

A total of 248 AEs were reported in 149 of the 687 subjects in the safety population (21.69%) during the 4 year surveillance period (Table 3 and Supplementary Table 9). The most frequent AEs by SOC were infections and infestations [14.26% (98/687) subjects, 126 events], and general disorders and administration site conditions [6.26% (43/687) subjects, 50 events] (Table 3). The most frequent preferred terms were nasopharyngitis [7.13% (49/687) subjects, 53 events] and pyrexia [4.80% (33/687) subjects, 35 events]. The list of all AEs within SOC is presented in Supplementary Table 9.

ARVs were reported in 25/687 participants (3.64%, 29 events). The most frequent SOC for ARVs was general disorders and administration site conditions [3.49% (24/687) subjects, 28 events] (Table 3). The most frequent preferred term was pyrexia [2.04% (14/687) subjects, 14 events]. The list of all ARVs within SOC is presented in Supplementary Table 9. All the ARVs were mild and recovered during the study period.

Of the AEs, 180 events in 116 participants (16.89%) were categorised as unexpected (Supplementary Table 10). The most common SOC for unexpected AEs was infections and infestations [14.26% (98/687) subjects, 126 events], and the most common preferred term was nasopharyngitis [7.13% (49/687) subjects, 53 events]. There was one unexpected ARV, injection site warmth, which was assessed by the investigator as mild with certain causal relationship with the study vaccine, and which resolved during the study period.

Four SAEs were reported in 3/687 subjects (0.44%). One subject had pneumonia, one had Kawasaki’s disease, and one subject reported exanthema subitum and febrile convulsion. All were categorised as unexpected, and none were considered a SARV. All four SAEs required hospitalisation, were graded as moderate and resolved within the study period.

Mild AEs accounted for 89.92%, moderate for 10.08% and there were no severe AEs. Regarding outcome, 93.15% (231/248 events) of AEs recovered, and the other AEs (6.85%, 17/248 events) were recovering/resolving. All of the recovering AEs were mild and were not evaluated as ARVs. There were no fatal events. Of the 248 AEs, 157 (63.31%) required a visit to or from medical personnel. Four (1.61%) required hospitalisation and were classed as SAEs; all resolved within the study period and were considered not related to the study vaccine. One subject went to the emergency room because of urticaria, but this event was not serious and was also assessed as not related to the study vaccine by the investigators.