Background
Methods
Design and participants
Objectives
Enrolment and randomization
Vaccines and vaccination
Assessments
Immunogenicity
Solicited AEs
Unsolicited AEs
Severity and causality of AEs
Statistical analyses
Results
Infants | Children | Adults | ||||
---|---|---|---|---|---|---|
6–35 months | 3–17 years | 18–49 years | ||||
IIV4-I N = 466 | IIV4 N = 474 | IIV4-I N = 410 | IIV4 N = 411 | IIV4-I N = 60 | IIV4 N = 60 | |
Mean age, (SD) | 19.7 (8.0) months | 19.9 (8.3) months | 9.4 (4.2) years | 9.4 (4.2) years | 29.8 (8.7) years | 31.2 (9.3) years |
Median age, (range) | 19 (4–36) months | 19 (5–35) months | 9.0 (3–18) years | 10.0 (3–18) years | 28.0 (19–49) years | 29.0 (18–49) years |
Male, n (%) | 243 (52.1) | 265 (55.9) | 214 (52.1) | 224 (54.5) | 19 (31.7) | 25 (41.7) |
White - Caucasian/European Heritage, n (%) | 329 (70.6) | 337 (71.1) | 378 (92.2) | 370 (90.0) | 60 (100) | 56 (93.3) |
African Heritage/African American, n (%) | 10(2.1) | 10 (2.1) | 11 (2.7) | 17 (4.1) | 0 | 2 (3.3) |
Asian - South East Asian Heritage, n (%) | 91 (19.5) | 91 (19.2) | 0 | 0 | 0 | 2 (3.3) |
White - Arabic/North African Heritage, n (%) | 28 (6.0) | 23 (4.9) | 13 (3.2) | 15 (3.6) | 0 | 0 |
Immunogenicity
Adults
Children
IIV4-I | IIV4 | IIV4/IIV4-I | |
---|---|---|---|
Adjusted GMT | Adjusted GMT | Adjusted GMT ratio (95% CI) | |
Infants, 6–35 months | N = 431 | N = 423a | |
A/H1N1 | 98.0 | 105.3 | 1.07 (0.90, 1.28) |
A/H3N2 | 47.7 | 56.3 | 1.18 (1.00, 1.39) |
B/Yamagata | 99.2 | 106.4 | 1.07 (0.91, 1.27) |
B/Victoria | 32.2 | 37.7 | 1.17 (0.99, 1.38) |
Children, 3–17 years | N = 403 | N = 402 | |
A/H1N1 | 707.3 | 684.9 | 0.97 (0.85, 1.11) |
A/H3N2 | 160.6 | 168.8 | 1.05 (0.94, 1.18) |
B/Yamagata | 496.0 | 509.4 | 1.03 (0.91, 1.16) |
B/Victoria | 240.8 | 250.4 | 1.04 (0.90, 1.21) |
Strain & cohort | Days | Seropositive | GMT | SPR | SCR | |||||
---|---|---|---|---|---|---|---|---|---|---|
n/N; % (95% CI) | value (95% CI) | n/N; % (95% CI) | n/N; % (95% CI) | |||||||
IIV4-I | IIV4 | IIV4-I | IIV4 | IIV4-I | IIV4 | IIV4-I | IIV4 | |||
A/H1N1 | Children | 0 | 354/403; 87.8 (84.2, 90.9) | 364/402; 90.5 (87.3, 93.2) | 80.2 (69.2, 93.0) | 87.7 (76.1, 101.0) | 308/403; 76.4 (72.0, 80.5) | 314/402; 78.1 (73.7, 82.1) | – | – |
56 or 28a | 402/403; 99.8 (98.6, 100) | 401/402; 99.8 (98.6, 100) | 698.0 (629.6, 773.9) | 694.1 (625.8, 769.7) | 393/403; 97.5 (95.5, 98.8) | 395/402; 98.3 (96.4, 99.3) | 274/403; 68.0 (63.2, 72.5) | 269/402; 66.9 (62.1, 71.5) | ||
Infants | 0 | 109/431; 25.3 (21.3, 29.7) | 111/424; 26.2 (22.1, 30.6) | 11.1 (9.6, 12.8) | 11.2 (9.7, 12.9) | 84/431; 19.5 (15.9, 23.5) | 83/424; 19.6 (15.9, 23.7) | – | – | |
56 or 28a | 406/432; 94.0 (91.3, 96.0) | 408/427; 95.6 (93.1, 97.3) | 97.5 (82.1, 115.7) | 105.5 (88.2, 126.1) | 303/432; 70.1 (65.6, 74.4) | 289/427; 67.7 (63.0, 72.1) | 287/431; 66.6 (61.9, 71.0) | 275/424; 64.9 (60.1, 69.4) | ||
A/H3N2 | Children | 0 | 346/403; 85.9 (82.1, 89.1) | 345/402; 85.8 (82.0, 89.1) | 38.9 (34.6, 43.8) | 41.9 (37.1, 47.3) | 245/403; 60.8 (55.8, 65.6) | 252/402; 62.7 (57.8, 67.4) | – | – |
56 or 28a | 400/403; 99.3 (97.8, 99.8) | 401/402; 99.8 (98.6, 100) | 158.2 (143.7, 174.2) | 171.4 (156.3, 188.0) | 377/403; 93.5 (90.7, 95.7) | 378/402; 94.0 (91.2, 96.1) | 192/403; 47.6 (42.7, 52.6) | 183/402; 45.5 (40.6, 50.5) | ||
Infants | 0 | 79/431; 18.3 (14.8, 22.3) | 91/423; 21.5 (17.7, 25.7) | 7.5 (6.8, 8.2) | 8.4 (7.5, 9.3) | 55/431; 12.8 (9.8, 16.3) | 67/423; 15.8 (12.5, 19.7) | – | – | |
56 or 28a | 388/432; 89.8 (86.6, 92.5) | 403/427; 94.4 (91.8, 96.4) | 45.2 (39.0, 52.3) | 59.9 (51.7, 69.4) | 232/432; 53.7 (48.9, 58.5) | 259/427; 60.7 (55.8, 65.3) | 217/431; 50.3 (45.5, 55.2) | 236/423; 55.8 (50.9, 60.6) | ||
B/Yamagata | Children | 0 | 325/403; 80.6 (76.4, 84.4) | 333/402; 82.8 (78.8, 86.4) | 58.1 (49.7, 68.0) | 70.8 (60.4, 83.0) | 266/403; 66.0 (61.2, 70.6) | 281/402; 69.9 (65.2, 74.3) | – | – |
56 or 28a | 403/403; 100 (99.1, 100) | 401/402; 99.8 (98.6, 100) | 479.0 (434.1, 528.5) | 527.6 (475.5, 585.3) | 396/403; 98.3 (96.5, 99.3) | 395/402; 98.3 (96.4, 99.3) | 273/403; 67.7 (62.9, 72.3) | 268/402; 66.7 (61.8, 71.3) | ||
Infants | 0 | 105/431; 24.4 (20.4, 28.7) | 99/423; 23.4 (19.4, 27.7) | 8.3 (7.5, 9.1) | 7.9 (7.2, 8.6) | 53/431; 12.3 (9.3, 15.8) | 49/423; 11.6 (8.7, 15.0) | – | – | |
56 or 28a | 415/432; 96.1 (93.8, 97.7) | 409/427; 95.8 (93.4, 97.5) | 100.8 (87.8, 115.8) | 105.4 (91.8, 121.0) | 329/432; 76.2 (71.9, 80.1) | 331/427; 77.5 (73.3, 81.4) | 318/431; 73.8 (69.4, 77.9) | 321/423; 75.9 (71.5, 79.9) | ||
B/Victoria | Children | 0 | 285/403; 70.7 (66.0, 75.1) | 287/402; 71.4 (66.7, 75.8) | 27.3 (23.8, 31.3) | 28.8 (25.0, 33.1) | 192/403; 47.6 (42.7, 52.6) | 195/402; 48.5 (43.5, 53.5) | – | – |
56 or 28a | 398/403; 98.8 (97.1, 99.6) | 394/402; 98.0 (96.1, 99.1) | 237.6 (210.4, 268.3) | 253.7 (222.7, 289.1) | 375/403; 93.1 (90.1, 95.3) | 374/402; 93.0 (90.1, 95.3) | 285/403; 70.7 (66.0, 75.1) | 287/402; 71.4 (66.7, 75.8) | ||
Infants | 0 | 30/431; 7.0 (4.7, 9.8) | 30/423; 7.1 (4.8, 10.0) | 5.7 (5.4, 6.1) | 5.7 (5.4, 6.1) | 17/431; 3.9 (2.3, 6.2) | 16/423; 3.8 (2.2, 6.1) | – | – | |
56 or 28a | 359/432; 83.1 (79.2, 86.5) | 366/427; 85.7 (82.0, 88.9) | 32.1 (28.1, 36.7) | 38.0 (33.2, 43.5) | 214/432; 49.5 (44.7, 54.4) | 217/427; 50.8 (46.0, 55.7) | 213/431; 49.4 (44.6, 54.2) | 211/423; 49.9 (45.0, 54.8) |
Infants
Reactogenicity and safety
Adults (18–49 years)
Infants | Children | Adults | ||||
---|---|---|---|---|---|---|
6–35 months | 3–17 years | 18–49 years | ||||
IIV4-I N = 466 | IIV4 N = 474 | IIV4-I N = 410 | IIV4 N = 411 | IIV4-I N = 60 | IIV4 N = 60 | |
Unsolicited AEs for 21 days (adults) or 28 days (infants & children) post-last vaccination | ||||||
≥1 AE, n (%) | 243 (52.1) | 262 (55.3) | 83 (20.2) | 86 (20.9) | 14 (23.3) | 14 (23.3) |
≥1 Grade 3 AE, n (%) | 33 (7.1) | 31 (6.5) | 12 (2.9) | 8 (1.9) | 3 (5.0) | 2 (3.3) |
≥1 AE causally-related to vaccination, n (%) | 6 (1.3) | 3 (0.6) | 10 (2.4) | 7 (1.7) | 2 (3.3) | 1(1.7) |
≥1 Grade 3 AE causally-related to vaccination, n (%) | 1 (0.2) [bronchitis] | 0 | 1 (0.2) [axillary pain] | 1 (0.2) [injection site pustule] | 0 | 0 |
MAEs for entire studya | ||||||
≥1 MAE, n (%) | 235 (50.4) | 252 (53.2) | 59 (14.4) | 52 (12.7) | 9 (15.0) | 8 (13.3) |
≥1 Grade 3 MAE, n (%) | 35 (7.5) | 29 (6.1) | 7 (1.7) | 6 (1.5) | 3 (5.0) | 1 (1.7) |
≥1 MAE causally-related to vaccination, n (%) | 2 (0.4) | 0 | 2 (0.5) | 0 | 0 | 0 |
≥1 Grade 3 MAE causally-related to vaccination, n (%) | 1 (0.2) [bronchitis] | 0 | 0 | 0 | 0 | 0 |
SAEs for entire studya | ||||||
≥1 SAE, n (%) | 7 (1.5) | 11 (2.3) | 1 (0.2) | 0 | 1 (1.7) | 1 (1.7) |
≥1 SAE causally-related to vaccination, n (%) | 0 | 0 | 0 | 0 | 0 | 0 |
Children (3–17 years)
Infants (6–35 months)
Axillary temperature, °C | IIV4-I n/N; % | IIV4 n/N; % | IIV4-I/IIV4 RR (95% CI) | p-value | |
---|---|---|---|---|---|
Dose 1 | ≥38.0 | 39/462; 8.4 | 42/ 470; 8.9 | 0.94 (0.59, 1.50) | 0.8851 |
Dose 2 | ≥38.0 | 40/420; 9.5 | 40/421; 9.5 | 1.00 (0.63, 1.59) | 1.000 |
Overall | ≥38.0 | 72/462; 15.6 | 69/470;14.7 | 1.06 (0.75, 1.50) | 0.7868 |