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