Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial - PubMed (original) (raw)

Clinical Trial

. 2020 Jun 13;395(10240):1845-1854.

doi: 10.1016/S0140-6736(20)31208-3. Epub 2020 May 22.

Yu-Hua Li 2, Xu-Hua Guan 3, Li-Hua Hou 4, Wen-Juan Wang 5, Jing-Xin Li 5, Shi-Po Wu 4, Bu-Sen Wang 4, Zhao Wang 3, Lei Wang 3, Si-Yue Jia 5, Hu-Dachuan Jiang 5, Ling Wang 2, Tao Jiang 6, Yi Hu 6, Jin-Bo Gou 7, Sha-Bei Xu 8, Jun-Jie Xu 4, Xue-Wen Wang 9, Wei Wang 10, Wei Chen 11

Affiliations

Clinical Trial

Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial

Feng-Cai Zhu et al. Lancet. 2020.

Abstract

Background: A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain.

Methods: We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127.

Findings: Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination.

Interpretation: The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation.

Funding: National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.

Copyright © 2020 Elsevier Ltd. All rights reserved.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Specific T-cell response measured by ELISpot (A) The number of specific T cells with secretion of IFNγ at days 0, 14, and 28 in all participants, and stratified by pre-existing Ad5 neutralising antibody titres. (B) The proportion of positive ELISpot responders at days 14 and 28 post-vaccination in all participants, and stratified by pre-existing Ad5 neutralising antibody titres. IFN=interferon. PBMCs=peripheral blood mononuclear cells. Ad5=adenovirus type-5. ELISpot=enzyme-linked immunospot.

Figure 2

Figure 2

Flow cytometry with intracellular cytokine staining before and after vaccination (A) Percentage of cells secreting IFNγ, TNFα, and IL-2 from CD4+ T cells. (B) Percentage of cells secreting IFNγ, TNFα, and IL-2 from CD8+ T cells. (C) The proportion of CD4+ T cells and CD8+ T cells producing any combination of IFNγ, TNFα, and IL-2. The analyses are for 108 participants, with 36 in each dose group. IFN=interferon. TNF=tumour necrosis factor. IL=interleukin.

Comment in

Similar articles

Cited by

References

    1. Zhu N, Zhang D, Wang W. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727–733. - PMC - PubMed
    1. Li Q, Guan X, Wu P. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med. 2020;382:1199–1207. - PMC - PubMed
    1. Grein J, Ohmagari N, Shin D. Compassionate use of remdesivir for patients with severe Covid-19. N Engl J Med. 2020 doi: 10.1056/NEJMoa2007016NEJMoa2007016. published online April 10. - DOI - PMC - PubMed
    1. Weiss P, Murdoch DR. Clinical course and mortality risk of severe COVID-19. Lancet. 2020;395:1014–1015. - PMC - PubMed
    1. WHO Coronavirus disease (COVID-2019) situation reports. 2020. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situatio...

Publication types

MeSH terms

Substances

LinkOut - more resources