Safety and immunogenicity of a modified COVID-19 mRNA vaccine,SYS6006,as a fourth-dose booster following three doses of inactivated vaccines in healthy adults:an open-labeled Phase 1 trial

The continuous emergence of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants led to a rapid decline in protection efficacy and neutralizing titers even after three doses of COVID-19 vaccines.Here,we report an open-labeled Phase I clinical trial of a modified mRNA vaccine(SYS6006)as a fourth-dose booster in healthy adults.Eighteen eligible participants,who had completed three doses of inactivated COVID-19 vaccines,received a fourth boosting dose of SYS6006-20μg.Eighteen convalescent COVID-19 patients were enrolled for the collection of serum samples as a comparator of immunogenicity.The primary endpoint of this trial was titers of anti-receptor binding domain of spike glycoprotein(RBD)antibodies of the Omicron strain(BA.2 and BA.4/5)in serum;titers of neutralizing antibodies against pseudovirus of the Omicron strain(BA.2 and BA.4/5).The secondary endpoint was the incidence of adverse events within 30 days after the boosting.The exploratory endpoint was the cellular immune responses(interferon gamma,IFN-γ).This trial was registered with the Chinese Clinical Trial Registry website.No serious adverse events were reported within 30 days after vaccination.No Grade 3 fever or serious adverse event was reported in the SYS6006 group.Notably,SYS6006 elicited higher titers and longer increases in anti-RBD antibodies and neutralizing antibodies(>90 days)compared with the convalescent group(P<0.0001)against Omicron strain(BA.2 and BA.4/5).Besides,higher positive spots of T-cell-secreting IFN-γwere observed in the SYS6006 group than those in the convalescent group(P<0.05).These data demonstrated that SYS6006 was well tolerated and highly immunogenic,generating a stronger and more durable immune response against different variants of SARS-CoV-2.