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

Type Journal Article Author Feng-Cai Zhu Author Xu-Hua Guan Author Yu-Hua Li Author Jian-Ying Huang Author Tao Jiang Author Li-Hua Hou Author Jing-Xin Li Author Bei-Fang Yang Author Ling Wang Author Wen-Juan Wang Author Shi-Po Wu Author Zhao Wang Author Xiao-Hong Wu Author Jun-Jie Xu Author Zhe Zhang Author Si-Yue Jia Author Bu-Sen Wang Author Yi Hu Author Jing-Jing Liu Author Jun Zhang Author Xiao-Ai Qian Author Qiong Li Author Hong-Xing Pan Author Hu-Dachuan Jiang Author Peng Deng Author Jin-Bo Gou Author Xue-Wen Wang Author Xing-Huan Wang Author Wei Chen URL https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31605-6/abstract Volume 396 Issue 10249 Pages 479-488 Publication The Lancet ISSN 0140-6736, 1474-547X Date 20/07/2020 Extra Publisher: Elsevier PMID: 32702299 Journal Abbr The Lancet DOI 10.1016/S0140-6736(20)31605-6 Library Catalog www.thelancet.com Language English Abstract 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 × 1011 viral particles per mL or 5 × 1010 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 × 1011 viral particles n=253; 5 × 1010 viral particles n=129) or placebo (n=126). In the 1 × 1011 and 5 × 1010 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 × 1011 and 5 × 1010 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 × 1011 and 5 × 1010 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 1011 viral particles dose group and one (1%) participant in the 5 × 1010 viral particles dose group. No serious adverse reactions were documented. Short Title Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older