Relative efficacy, safety, and immunogenicity analysis of two doses versus one dose of recombinant coronavirus vaccine (adenovirus type 5 vector) in adults 18 years and older: an international, multicentre, randomized, double blinded phase 3 trial

An international, double-blind, placebo-controlled phase 3 study in healthy adults previously showed one dose of the Ad5-nCoV vaccine was efficacious (57.5%) against symptomatic COVID-19 infection, especially severe disease, was safe, and immunogenic ( ClinicalTrials.gov , NCT04526990 ). The current study extends that report to assess relative vaccine efficacy (rVE), safety, and immunogenicity of two doses versus one dose of Ad5-nCoV vaccine. Participants from the prior (part-one) study who continued to the follow-up study (part-two) herein were provided an Ad5-nCoV dose at study sites in Argentina, Chile, Mexico, Pakistan, and Russia, starting June 8th 2021 (median = 6 months post-first-injection). This injection led to two doses and one dose received by the prior vaccine and placebo recipients, respectively. Participants were monitored for COVID-19 disease, safety, and antibody responses up to 24 weeks post-vaccination. The endpoint of 83 cases occurred August 9, 2021, triggering primary efficacy analysis which evaluated rVE ≥10% (two versus one dose) of Ad5-nCoV in preventing PCR-confirmed COVID-19 disease at least 28 days post-vaccination. rVE (34.12%) was non-significant (95% CI −1.31 to 57.15, n = 8266), indicating similar efficacy of dose groups. End-of-study analysis (cutoff January 28, 2022) showed rVE was 6.3% (95% CI −8.7 to 19.2, starting 28 days), and for severe disease was 79.5% (95% CI 28.1% to 94.2%, starting 28 days). Serious adverse events (SAEs, ≥grade 4) were more frequent after one dose (12 [0.12%]) than two doses (4 [0.04%], p = 0.043), as were medically attended adverse events (9 [0.090%] and 1 [0.009%], p = 0.009). One SAE (myocarditis) was related to the study-product. Spike-RBD IgG and neutralization antibody titers were elevated for two-dose versus one-dose recipients (1.7- and 4.4-fold) at 28-days post-vaccination. Antibody responses waned by 24 weeks. Two doses and one dose of Ad5-nCoV vaccine are efficacious, safe and immunogenic. A second dose improves protection against severe disease and immunogenicity. The trial is registered at ClinicalTrials.gov ( NCT04526990 ). • Two doses of Ad5-nCoV have similar efficacy as one dose. • Vaccine efficacy lost over time following one dose is restored by a second dose. • A second vaccine dose improves protection against severe disease and immunogenicity. • Two doses, and one dose, of Ad5-nCoV are each efficacious, safe and immunogenic.