Safety, tolerability, and immunogenicity of a CpG/Alum adjuvanted SARS-CoV-2 recombinant protein vaccine (ZR202-CoV) in healthy adults: Preliminary report of a phase 1, randomized, double-blind, placebo-controlled, dose-escalation trial.

ABSTRACT

This was a phase 1 dose-escalation study of ZR202-CoV, a recombinant protein vaccine candidate containing a pre-fusion format of the spike (S)-protein (S-trimer) combined with the dual-adjuvant system of Alum/CpG. A total of 230 participants were screened and 72 healthy adults aged 18-59 years were enrolled and randomized to receive two doses at a 28-day interval of three different ZR202-CoV formulations or normal saline. We assessed the safety for 28 days after each vaccination and collected blood samples for immunogenicity evaluation. All formulations of ZR202-CoV were well-tolerated, with no observed solicited adverse events ≥ Grade 3 within 7 days after vaccination. No unsolicited adverse events ≥ Grade 3, or serious adverse events related to vaccination occurred as determined by the investigator. After the first dose, detectable immune responses were observed in all subjects. All subjects that received ZR202-CoV seroconverted at 14 days after the second dose by S-binding IgG antibody, pseudovirus and live-virus based neutralizing antibody assays. S-binding response (GMCs 2708.7 ~ 4050.0 BAU/mL) and neutralizing activity by pseudovirus (GMCs 363.1 ~ 627.0 IU/mL) and live virus SARS-CoV-2 (GMT 101.7 ~ 175.0) peaked at 14 days after the second dose of ZR202-CoV. The magnitudes of immune responses compared favorably with COVID-19 vaccines with reported protective efficacy.