Long-Term Immunogenicity Study of an Aluminum Phosphate-Adjuvanted Inactivated Enterovirus A71 Vaccine in Children: An Extension to a Phase 2 Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Participants
2.2. Randomization and Blinding
2.3. Procedure and Outcomes
- Geometric mean titer (GMT) of EV-A71 neutralizing antibody titers at 4 years and 5 years after the first dose of vaccination for part 2b; and 3 years to 5 years after the first dose of vaccination for parts 2c and 2d.
- Seroprotection rate (defined as neutralizing antibody titer ≥1:32) at 4 years and 5 years after the first dose of vaccination for part 2b; and 3 years to 5 years after the first dose of vaccination for parts 2c and 2d.
2.4. Statistical Analysis
- The ITF population included all enrolled subjects for whom data are available.
- The ATP population for analysis of immunogenicity included all evaluable subjects (i.e., those meeting all eligibility criteria and complied with the procedures defined in the protocol during the study) for whom data concerning immunogenicity endpoint measures are available.
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Group 2b (2–6 Years Old at Time of 1st Dose) | Group 2c (6 Months–2 Years Old at Time of 1st Dose) | Group 2d (2–6 Months Old at Time of 1st Dose) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Placebo | LD | MD | HD | Placebo | MD | HD | Placebo | MD | HD | |
N | 22 | 23 | 24 | 22 | 12 | 31 | 33 | 8 | 26 | 26 |
Age at time of screening (Mean years, SD) * | 8.5 (1.26) | 9.0 (1.14) | 8.2 (1.1) | 8.6 (1.1) | 5.5 (0.26) | 5.2 (0.36) | 5.2 (0.40) | 4.0 (0.16) | 4.1 (0.14) | 4.1 (0.14) |
Male/Female (number of participants) | 11/11 | 14/9 | 16/8 | 10/12 | 6/6 | 15/16 | 20/13 | 4/4 | 12/14 | 9/17 |
Duration from first vaccination (Mean years, SD) | 4.3 (0.07) | 4.4 (0.07) | 4.4 (0.07) | 4.2 (0.07) | 4.0 (0.09) | 3.9 (0.12) | 3.9 (0.12) | 3.7 (0.13) | 3.8 (0.14) | 3.8 (0.12) |
Group 2b (2–6 Years Old at Time of 1st Dose) | Group 2c (6 Months–2 Years Old at Time of 1st Dose) | Group 2d (2–6 Months Old at Time of 1st Dose) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Placebo | LD | MD | HD | Placebo | MD | HD | Placebo | MD | HD | |
Year 3 (Day 1096) | ||||||||||
N | - | - | - | - | 12 | 31 | 33 | 8 | 26 | 26 |
GMT (95% CI) * | - | - | - | - | 8.22 (2.75–24.56) | 1206.99 (842.55–1729.05) | 1576.81 (1171.27–2122.77) | 7.64 (1.65–35.28) | 813.72 (538.80–1228.92) | 956.17 (564.73–1618.93) |
Year 4 (Day 1461) | ||||||||||
N | 22 | 23 | 24 | 22 | 12 | 31 | 32 | 7 | 24 | 25 |
GMT (95% CI) * | 9.25 (4.06–21.08) | 367.30 (227.23–593.70) | 430.38 (258.53–716.49) | 558.24 (359.16–867.66) | 8.69 (2.68–28.17) | 1653.18 (1178.10–2319.83) | 2501.62 (1837.26–3406.21) | 10.28 (1.80–58.92) | 1007.61 (609.16–1666.71) | 1699.14 (1141.13–2530.02) |
Year 5 (Day 1826) | ||||||||||
N | 21 | 23 | 23 | 22 | 12 | 30 | 33 | 7 | 24 | 24 |
GMT (95% CI) * | 9.82 (4.09–23.57) | 621.38 (398.89–967.96) | 978.20 (588.34–1626.40) | 910.48 (549.55–1508.47) | 7.90 (2.78–22.43) | 841.40 (624.89–1132.92) | 1159.93 (849.04–1584.64) | 7.40 (1.64–33.23) | 477.71 (284.84–801.17) | 745.07 (469.41–1182.60) |
Group 2b (2–6 Years Old at Time of 1st Dose) | Group 2c (6 Months–2 Years Old at Time of 1st Dose) | Group 2d (2–6 Months Old at Time of 1st Dose) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Placebo | LD | MD | HD | Placebo | MD | HD | Placebo | MD | HD | |
Year 3 (Day 759) | ||||||||||
N | - | - | - | - | 12 | 31 | 33 | 8 | 26 | 26 |
Number of seroprotected participants (NAb ≥ 1:32) | - | - | - | - | 2 | 31 | 33 | 1 | 26 | 25 |
SPR (95% CI **) | - | - | - | - | 16.7 (2.09–48.41) | 100.00 (88.78–100.00) | 100.00 (89.42–100.00) | 12.5 (0.32–52.65) | 100.00 (86.77–100.00) | 96.2 (80.36–99.90) |
Year 4 (Day 1461) | ||||||||||
N | 22 | 23 | 24 | 22 | 12 | 31 | 32 | 7 | 24 | 25 |
Number of seroprotected participants (NAb ≥ 1:32) | 4 | 22 | 24 | 22 | 2 | 31 | 32 | 1 | 24 | 25 |
SPR (95% CI **) | 18.18 (5.19–40.28) | 95.65 (78.05–99.89) | 100.00 (85.75–100.00) | 100.00 (84.56–100.00) | 16.7 (2.09–48.41) | 100.00 (88.78–100.00) | 100.00 (89.11–100.00) | 14.3 (0.36–57.87) | 100.00 (85.75–100.00) | 100.00 (86.28–100.00) |
Year 5 (Day 1826) | ||||||||||
N | 21 | 23 | 23 | 22 | 12 | 30 | 33 | 7 | 24 | 24 |
Number of seroprotected participants (NAb ≥ 1:32) | 4 | 23 | 23 | 22 | 2 | 30 | 33 | 1 | 23 | 24 |
SPR* (95% CI **) | 19.05 (5.45–41.91) | 100.00 (85.18–100.00) | 100.00 (85.18–100.00) | 100.00 (84.56–100.00) | 16.7 (2.09–48.41) | 100.00 (88.43–100.00) | 100.00 (89.42–100.00) | 14.3 (0.36–57.87) | 95.8 (78.88–99.89) | 100.00 (85.75–100.00) |
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Chiu, N.-C.; Lin, C.-Y.; Chen, C.; Cheng, H.-Y.; Hsieh, E.-F.; Liu, L.T.-C.; Chiu, C.-H.; Huang, L.-M. Long-Term Immunogenicity Study of an Aluminum Phosphate-Adjuvanted Inactivated Enterovirus A71 Vaccine in Children: An Extension to a Phase 2 Study. Vaccines 2024, 12, 985. https://doi.org/10.3390/vaccines12090985
Chiu N-C, Lin C-Y, Chen C, Cheng H-Y, Hsieh E-F, Liu LT-C, Chiu C-H, Huang L-M. Long-Term Immunogenicity Study of an Aluminum Phosphate-Adjuvanted Inactivated Enterovirus A71 Vaccine in Children: An Extension to a Phase 2 Study. Vaccines. 2024; 12(9):985. https://doi.org/10.3390/vaccines12090985
Chicago/Turabian StyleChiu, Nan-Chang, Chien-Yu Lin, Charles Chen, Hao-Yuan Cheng, Erh-Fang Hsieh, Luke Tzu-Chi Liu, Cheng-Hsun Chiu, and Li-Min Huang. 2024. "Long-Term Immunogenicity Study of an Aluminum Phosphate-Adjuvanted Inactivated Enterovirus A71 Vaccine in Children: An Extension to a Phase 2 Study" Vaccines 12, no. 9: 985. https://doi.org/10.3390/vaccines12090985