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Supplemental digital content 2.

Hemagglutination-inhibition antibody responses by vaccine and priming status in the per-protocol immunogenicity cohort

A/H1N1 A/H3N2 B/Victoria B/Yamagata

GMT N; value (95% CI)

QIV primed Day 0 94; 40.3

(27.0–60.2)

94; 22.8 (16.7–31.2)

94; 8.9 (7.2–11.0)

94; 29.3 (23.0–37.4) Day 28 94; 117.0

(83.2–164.5)

94; 85.2 (64.8–112.0)

94; 38.7 (26.2–57.1)

94; 243.6 (198.1–299.6) QIV unprimed Day 0 190; 14.7

(11.8–18.4)

192; 17.7 (14.1–22.1)

190; 7.8 (6.7–9.2)

188; 9.1 (7.7–10.7) Day 28 97; 173.1

(113.1–264.8)

96; 99.3 (64.8–152.2)

95; 26.5 (17.7–39.7)

97; 97.0 (64.7–145.4) Day 56 99; 253.1

(203.4–314.8)

99; 168.1 (136.6–206.7)

98; 97.2 (74.9–126.1)

99; 311.1 (255.4–379.1)

TIV primed Day 0 95; 36.5

(24.3–54.9)

95; 21.7 (16.0–29.5)

95; 9.7 (7.7–12.4)

95; 37.7 (29.8–47.8) Day 28 95; 124.4

(89.8–172.4)

95; 83.0 (63.6–108.2)

95; 44.0 (29.6–65.2)

95; 127.2 (106.1–152.3) TIV unprimed Day 0 198; 12.8

(10.5–15.7)

197; 17.9 (14.1–22.6)

198; 8.7 (7.5–10.3)

198; 9.9 (8.4–11.8) Day 28 101; 161.6

(103.9–251.4)

101; 84.2 (54.1–131.2)

101; 34.6 (22.4–53.6)

102; 30.0 (21.3–42.1) Day 56 98; 249.0

(192.5–321.9)

98; 202.1 (158.6–257.5)

98; 99.6 (76.7–129.4)

98; 42.2 (30.6–58.1)

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A/H1N1 A/H3N2 B/Victoria B/Yamagata SPR

n/N; % (95% CI) QIV primed Day 0 48/94; 51.1

(40.5–61.5)

39/94; 41.5 (31.4–52.1)

16/94; 17.0 (10.1–26.2)

56/94; 59.6 (49.0–69.6) Day 28 73/94; 77.7

(67.9–85.6)

75/94; 79.8 (70.2–87.4)

50/94; 53.2 (42.6–63.6)

91/94; 96.8 (91.0–99.3) QIV unprimed Day 0 58/190; 30.5

(24.1–37.6)

74/192; 38.5 (31.6–45.8)

25/190; 13.2 (8.7–18.8)

37/188; 19.7 (14.3–26.1) Day 28 76/97; 78.4

(68.8–86.1)

64/96; 66.7 (56.3–76.0)

36/95; 37.9 (28.1–48.4)

67/97; 69.1 (58.9–78.1) Day 56 95/99; 96.0

(90.0–98.9)

96/99; 97.0 (91.4–99.4)

84/98; 85.7 (77.2–92.0)

98/99; 99.0 (94.5–100) TIV primed Day 0 45/95; 47.4

(37.0–57.9)

36/95; 37.9 (28.1–48.4)

20/95; 21.1 (13.4–30.6)

62/95; 65.3 (54.8–74.7) Day 28 78/95; 82.1

(72.9–89.2)

80/95; 84.2 (75.3–90.9)

52/95; 54.7 (44.2–65.0)

90/95; 94.7 (88.1–98.3) TIV unprimed Day 0 54/198; 27.3

(21.2–34.0)

70/197; 35.5 (28.9–42.6)

35/198; 17.7 (12.6–23.7)

40/198; 20.2 (14.8–26.5) Day 28 78/101; 77.2

(67.8–85.0)

61/101; 60.4 (50.2–70.0)

41/101; 40.6 (30.9–50.8)

53/102; 52.0 (41.8–62.0) Day 56 94/98; 95.9

(89.9–98.9)

94/98; 95.9 (89.9–98.9)

88/98; 89.8 (82.0–95.0)

59/98; 60.2 (49.8–70.0)

A/H1N1 A/H3N2 B/Victoria B/Yamagata

SCR n/N; % (95% CI) QIV primed Day 28 30/94; 31.9

(22.7–42.3)

48/94; 51.1 (40.5–61.5)

46/94; 48.9 (38.5–59.5)

82/94; 87.2 (78.8–93.2) QIV unprimed Day 28 63/95; 66.3 55/96; 57.3 34/94; 36.2 59/93; 63.4

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(55.9–75.7) (46.8–67.3) (26.5–46.7) (52.8–73.2) Day 56 81/95; 85.3

(76.5–91.7)

79/96; 82.3 (73.2–89.3)

77/95; 81.1 (71.7–88.4)

90/95; 94.7 (88.1–98.3)

TIV primed 39/95; 41.1

(31.1–51.6)

46/95; 48.4 (38.0–58.9)

42/95; 44.2 (34.0–54.8)

40/95; 42.1 (32.0–52.7) TIV unprimed Day 28 74/101; 73.3

(63.5–81.6)

54/100; 54.0 (43.7–64.0)

40/101; 39.6 (30.0–49.8)

40/101; 39.6 (30.0–49.8) Day 56 89/97; 91.8

(84.4–96.4)

75/97; 77.3 (67.7–85.2)

85/97; 87.6 (79.4–93.4)

42/97; 43.3 (33.3–53.7)

A/H1N1 A/H3N2 B/Victoria B/Yamagata

SCF N; value (95% CI) QIV primed Day 28 94; 2.9

(2.3–3.6)

94; 3.7 (3.1–4.5)

94; 4.4 (3.3–5.8)

94; 8.3 (6.8–10.1) QIV unprimed Day 28 95; 9.9

(7.0–14.1)

96; 4.9 (3.7–6.3)

94; 3.6 (2.7–5.0)

93; 9.9 (6.9–14.0) Day 56 95; 19.8

(15.4–25.6)

96; 11.1 (9.0–13.7)

95; 11.3 (9.4–13.6)

95; 35.1 (27.6–44.6) TIV primed Day 28 95; 3.4

(2.7–4.2)

95; 3.8 (3.1–4.7)

95; 4.5 (3.4–6.0)

95; 3.4 (2.8–4.0) TIV unprimed Day 28 101; 12.7

(9.1–17.7)

100; 5.1 (3.9–6.7)

101; 3.8 (2.9–5.0)

101; 3.4 (2.5–4.5) Day 56 97; 19.2

(15.2–24.2)

97; 10.3 (8.3–12.9)

97; 12.1 (9.8–14.8)

97; 3.7 (2.9–4.8) CI, confidence interval; GMT, geometric mean titer; SPR, seroprotection rate; SCR, seroconversion rate; SCF, seroconversion factor; QIV, inactivated quadrivalent influenza vaccine; TIV, inactivated trivalent influenza vaccine; N refers to total population assessed at specified time-point; n refers to number of subjects fulfilling definition of the outcome measure; SPR defined as proportion of children with HI antibody titers ≥1:40; SCR defined as proportion of children with a pre-vaccination HI antibody titer <1:10 and post-vaccination HI antibody titer ≥1:40, or children with at least a 4-fold increase in the post-vaccination HI antibody titer; SCF defined as the geometric mean of the within children ratios of reciprocal HI antibody titers for post-vaccination versus pre-vaccination; ‘Primed’ and ‘unprimed’ children were and were not enrolled in a study during the preceding season where they received TIV, respectively; In the primed cohort, antibody responses were assessed

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at Day 28; In the unprimed cohort, antibody responses were assessed in half of the population at Day 28 (after dose 1) and in the other half of the population at Day 56 (after dose 2)

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