Pooled Analysis of the Effect of Pre-Existing Ad5 Neutralizing Antibodies on the Immunogenicity of Adenovirus Type 5 Vector-Based COVID-19 Vaccine from Eight Clinical Trials
Abstract
:1. Introduction
2. Methods
2.1. Study Design and Data Source
2.2. Antibody Detection
2.3. Statistical Analysis
3. Results
3.1. Study Population
3.2. Impact of Pre-Existing Ad5 NAbs on Live SARS-CoV-2 NAbs After Receiving Ad5-nCoV as a Primary Immunization Strategy
3.3. Impact of Pre-Existing Ad5 NAbs on Live SARS-CoV-2 NAbs After Receiving Ad5-nCoV as a Heterologous Boosting Immunization Strategy
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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Immunization Schedule [Dosage] | 6–17 Years a | 18 Years or Older a | |
---|---|---|---|
Ad5-IM-prime | Ad5-IM [3.0 × 1010 vp] | NCT04916886 | / |
Ad5-IM [5.0 × 1010 vp] | / | NCT04313127 NCT04341389 NCT04916886 | |
Ad5-IM [1.0 × 1011 vp] | / | NCT04313127 NCT04341389 | |
Ad5-IM [1.5 × 1011 vp] | / | NCT04313127 | |
Ad5-IM-boost | ICV × 2 + Ad5-IM [3.0 × 1010 vp] | NCT05330871 | / |
ICV × 1 + Ad5-IM [5.0 × 1010 vp] | / | NCT04892459 NCT04952727 | |
ICV × 2 + Ad5-IM [5.0 × 1010 vp] | / | NCT04892459 NCT04952727 | |
ICV × 3 + Ad5-IM [5.0 × 1010 vp] | / | NCT05303584 | |
Ad5-IH-boost | ICV × 2 + Ad5-IH [1.0 × 1010 vp] | NCT05330871 | NCT05043259 |
ICV × 2 + Ad5-IH [2.0 × 1010 vp] | / | NCT05043259 | |
ICV × 3 + Ad5-IH [1.0 × 1010 vp] | / | NCT05303584 |
Ad5-IM-Prime | Ad5-IM-Boost | Ad5-IH-Boost | p Value | |
---|---|---|---|---|
Adolescent cohort, ages 6–17 years (N = 1273) | ||||
Participants, n | 1001 | 65 | 207 | / |
Median age (IQR) | 12.0 (10.0, 14.0) | 13.0 (9.0, 14.0) | 12.0 (10.0, 14.0) | 0.6141 |
Sex (%) | ||||
Male | 542 (54.1%) | 31 (47.7%) | 103 (49.8%) | 0.3446 |
Female | 459 (45.9%) | 34 (52.3%) | 104 (50.2%) | |
Pre-existing Ad5 neutralising antibodies | ||||
Geometric mean titers (95% CI) | 118.3 (101.7, 137.6) | 73.0 (37.1, 143.7) | 116.4 (81.5, 166.0) | 0.3146 |
Participants with titers < 1:12 (%) | 336 (33.6%) | 32 (49.2%) | 76 (36.7%) | 0.0008 |
1:12 ≤ Participants with titers ≤ 1:200 (%) | 114 (11.4%) | 7 (10.8%) | 21 (10.1%) | |
1:200 < Participants with titers ≤ 1:1000 (%) | 425 (42.4%) | 13 (20.0%) | 69 (33.3%) | |
Participants with titers > 1:1000 (%) | 126 (12.6%) | 13 (20.0%) | 41 (19.8%) | |
Adult cohort, ages 18 years and older (N = 2239) | ||||
Participants, n | 1450 | 396 | 393 | / |
Median age (IQR) | 42.0 (33.0, 50.0) | 53.0 (44.0, 65.0) | 43.0 (35.0, 50.0) | <0.0001 |
Sex (%) | ||||
Male | 749 (51.7%) | 215 (54.3%) | 171 (43.5%) | 0.0048 |
Female | 701 (48.3%) | 181 (45.7%) | 222 (56.5%) | |
Pre-existing Ad5 neutralising antibodies | ||||
Geometric mean titers (95% CI) | 146.5 (131.5, 163.3) | 165.7 (134.8, 203.8) | 236.8 (189.9, 295.1) | 0.0004 |
Participants with titers < 1:12 (%) | 297 (20.5%) | 66 (16.7%) | 59 (15.0%) | 0.0026 |
1:12 ≤ Participants with titers ≤ 1:200 (%) | 364 (25.1%) | 109 (27.5%) | 94 (23.9%) | |
1:200 < Participants with titers ≤ 1:1000 (%) | 593 (40.9%) | 175 (44.2%) | 160 (40.7%) | |
Participants with titers > 1:1000 (%) | 200 (13.8%) | 46 (11.6%) | 80 (20.4%) |
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Liu, W.; Li, Y.; Li, X.; Wang, F.; Qi, R.; Zhu, T.; Li, J. Pooled Analysis of the Effect of Pre-Existing Ad5 Neutralizing Antibodies on the Immunogenicity of Adenovirus Type 5 Vector-Based COVID-19 Vaccine from Eight Clinical Trials. Vaccines 2025, 13, 333. https://doi.org/10.3390/vaccines13030333
Liu W, Li Y, Li X, Wang F, Qi R, Zhu T, Li J. Pooled Analysis of the Effect of Pre-Existing Ad5 Neutralizing Antibodies on the Immunogenicity of Adenovirus Type 5 Vector-Based COVID-19 Vaccine from Eight Clinical Trials. Vaccines. 2025; 13(3):333. https://doi.org/10.3390/vaccines13030333
Chicago/Turabian StyleLiu, Wenqing, Yuqing Li, Xiaolong Li, Feiyu Wang, Runjie Qi, Tao Zhu, and Jingxin Li. 2025. "Pooled Analysis of the Effect of Pre-Existing Ad5 Neutralizing Antibodies on the Immunogenicity of Adenovirus Type 5 Vector-Based COVID-19 Vaccine from Eight Clinical Trials" Vaccines 13, no. 3: 333. https://doi.org/10.3390/vaccines13030333
APA StyleLiu, W., Li, Y., Li, X., Wang, F., Qi, R., Zhu, T., & Li, J. (2025). Pooled Analysis of the Effect of Pre-Existing Ad5 Neutralizing Antibodies on the Immunogenicity of Adenovirus Type 5 Vector-Based COVID-19 Vaccine from Eight Clinical Trials. Vaccines, 13(3), 333. https://doi.org/10.3390/vaccines13030333