Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial
Open accessAbstract
Background This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an appropriate dose of the candidate vaccine for an efficacy study. Methods This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 10 11 viral particles per mL or 5 × 10 10 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389. Findings 603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 10 11 viral particles n=253; 5 × 10 10 viral particles n=129) or placebo (n=126). In the 1 × 10 11 and 5 × 10 10 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2-749·2) and 571·0 (467·6-697·3), with seroconversion rates at 96% (95% CI 93-98) and 97% (92-99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8-22·7) and 18·3 (14·4-23·3) in participants receiving 1 × 10 11 and 5 × 10 10 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85-93) of 253 and 113 (88%, 81-92) of 129 participants in the 1 × 10 11 and 5 × 10 10 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 10 11 and 5 × 10 10 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 10 11 viral particles dose group and one (1%) participant in the 5 × 10 10 viral particles dose group. No serious adverse reactions were documented. Interpretation The Ad5-vectored COVID-19 vaccine at 5 × 10 10 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation. Funding National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics.
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Long-term homologous prime-boost with identical viral-vectored vaccines may be limited by anti-vector immunity.
“In the long term, a strategy involving homologous prime–boost with identical viral-vectored vaccines may be limited by anti-vector immunity12,91,92.”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [91]
Gam-COVID-Vac uses different adenovirus vectors for each dose, which circumvents anti-vector immunity that could inhibit anti-S responses, as seen with Ad5-nCoV and non-COVID-19 adenovirus-based vaccines.
“This may be, in part, due to the fact that Gam-COVID-Vac uses different adenovirus vectors for each dose (adenovirus 26 for dose one and adenovirus 5 for dose two), thus circumventing the potential problem of anti-vector immunity that could inhibit anti-S responses, as has been identified for Ad5-nCoV (refs12,91) (Table 1) and non-COVID-19 adenovirus-based vaccines92.”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [91]
CD8+ T cell responses to candidate COVID-19 vaccines in humans or non-human primates are either largely absent or not measured in the current literature.
“CD8+ T cell responses to candidate COVID-19 vaccines in humans or non-human primates are either largely absent or not measured in the current literature”
From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as Zhu et al., 2020
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- Authors
- Zhu, F.-C., Guan, X.-H., Li, Y.-H., Huang, J.-Y., Jiang, T., Hou, L.-H., Li, J.-X., Yang, B.-F., Wang, L., Wang, W.-J., Wu, S.-P., Wang, Z., Wu, X.-H., Xu, J.-J., Zhang, Z., Jia, S.-Y., Wang, B.-S., Hu, Y., Liu, J.-J., Zhang, J., Qian, X.-A., Li, Q., Pan, H.-X., Jiang, H.-D., Deng, P., Gou, J.-B., Wang, X.-W., Wang, X.-H., & Chen, W.
- Affiliations
- Hubei Provincial Center for Disease Control and Prevention (CN)
- National Institutes for Food and Drug Control (CN)
- Zhongnan Hospital of Wuhan University (CN)
- Beijing Institute of Microbiology and Epidemiology (CN)
- Academy of Military Medical Sciences (CN)
- Jiangsu Provincial Center for Disease Control and Prevention (CN)
- CanSino (China) (CN)
- Corresponding author
- Chen, Wei
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 396
- Issue
- 10249
- Pages
- 479-488
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- PMC
- PMC7836858
- OpenAlex
- W3042383115
- Cited by
- 1,225
- References
- 21
- Citations by year
- 2026: 16 · 2025: 44 · 2024: 79 · 2023: 149 · 2022: 253 · 2021: 489 · 2020: 193
- FWCI
- 35.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Lancet (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- reponame:Expeditio Repositorio Institucional UJTL
- Funders
- Wuhan University
- Zhongnan Hospital of Wuhan University
- National Science and Technology Major Project
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- adenovirus type 5 vector, COVID-19 vaccines, SARS-CoV-2, vaccine immunogenicity, vaccine safety, dose comparison, neutralizing antibodies, receptor-binding domain antibodies, antibody response, adverse events, healthy adults, Wuhan, China
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, COVID-19 Vaccines, Adenoviridae, Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Antibodies, Viral, China, Double-Blind Method, Female, Genetic Vectors, Humans, Male, Middle Aged, Pneumonia, Viral, T-Lymphocytes, Viral Vaccines, Coronavirus Infections, Young Adult, Antibodies, Neutralizing, Pandemics, Spike Glycoprotein, Coronavirus
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