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

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 × 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 (7...

Prime-boost vaccination of mice and Rhesus macaques with two novel adenovirus vectored COVID-19 vaccine candidates

“…1D). However, the pre-existing anti-Ad5 immunity might partly limit vaccine effectiveness, especially for populations aged over 50 ( 8,9,24,25 ), while the low seroprevalence of antibodies to novel adenoviral vectors such as ChAdox1 ( 11 ), Ad26 ( 12,14,21,27 ), and Sad23L and Ad49L used in this study might avoid a negative impact on vaccine efficacy ( 22–24 ).…”

“…Thirdly, in order to achieve an effective vaccine immunity, a low dose of two heterologous adenovirus vectored vaccines (<5×10 10 vp) with prime-boost immunization regimen should theoretically reduce severe adverse reaction induced by a high dose of adenovirus vectored vaccine (>5×10 10 vp) with prime only immunization in clinical trials ( 8,9,11,14 ). In this study, a relatively low dose of Sad23L-nCoV-S and Ad49L-nCoV-S vaccines elicited a robust immunity in both young mice and older rhesus macaques (aged 11-14 years), but no obvious clinical symptoms or histopathological changes were observed (Fig.…”

Covid-19: Where are we on immunity and vaccines?

“…The second paper came from researchers in China, who tested their non-replicating adenovirus type-5 vectored vaccine (Ad5-nCoV) on 382 participants (who received either a high or low dose, while 126 people received a placebo) 3. This vaccine candidate, developed with CanSino Biologics, uses a weakened human common cold virus to deliver genetic material that codes for the SARS-CoV-2 spike protein to the cells.…”

Russian SARS-CoV-2 vaccine

“…No “serious complications or side effects” were reported in the phase II trials,1 but they included only a small number of healthy participants. More extensive testing has been performed for a similar Ad5 based covid-19 vaccine in Wuhan, where no serious adverse events were documented in 382 healthy volunteers 5. But neither vaccine has been tested in people with pre-existing health conditions, who are arguably most in need of protection.…”