Reduced Binding Activity of Vaccine Serum to Omicron Receptor-Binding Domain

Background: Coronavirus disease 2019 (COVID-19) vaccination regimens contribute to limiting the spread of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). But the emergence and the rapid spread of the SARS-CoV-2 variant Omicron raise concerns about the efficacy of the current vaccination strategy. The binding activity of vaccine serum to virus receptor-binding domain (RBD) represents a correlation of protection against virus infection. We here investigated the reactivity of anti-sera from Chinese subjects immunized with SARS-CoV-2 vaccines to a variety of recombinant RBDs.Methods: Monomeric and dimeric RBDs of the spike protein of prototype SARS-CoV-2 and Omicron variant were separately cloned and expressed in E.coli. 106 human serum samples from 91 participants from Jiangxi, China, were collected and identified for the presence of SARS-CoV-2 antibodies by Lateral Flow Dipstick (LFD) and ELISA. LFD-positive data for vaccinated human sera between different groups stratified by boost time and age were compared by chi-square test. The cross-reactivity of SARS-CoV-2 antibody-positive sera from prototype SARS-CoV-2 vaccine immunized individuals to a variety of recombinant RBDs was examined by ELISA.Findings: All recombinant RBDs were successfully expressed in E.coli. LFD assays identified 26 SARS-CoV-2 antibody-positive sera from 106 human serum samples. Vaccine sera collected at 7 days to one month after boost have a higher LFD-positive rate than those collected within one week after boost (P<0.0001). Interestingly, vaccine sera from Children have a higher positive rate than those from adult in our tested samples (P=0.0073). ELISA showed the elegant reactivity of SARS-CoV-2 antibody-positive sera from prototype SARS-CoV-2 vaccine immunized individuals to its homogenous monomeric and dimeric RBDs, whereas the reactivity to Omicron RBD monomer and dimer decreased by 1.25 to 1.71-fold.Interpretation: The lower binding activity of Omicron RBD to SARS-CoV-2-vaccine immunized human serum implies less efficacy of the SARS-CoV-2 vaccine to protect against Omicron variant than its cognate virus.Funding: This study was funded by research grants from National Natural Science Foundation of China (grants 31460667, 31860038, and 31960699), Key scientific and Technological projects of Jiangxi Province (20161BBF60084), Education Department foundations of Jiangxi Province (grants GJJ180239, and GJJ200405), Startup fund from Jiangxi Agriculture University (9232307726).Declaration of Interest: None to declare. Ethical Approval: All studies involving human sera were performed in accordance with the standards of Jiangxi Agriculture University Ethical Committee with the protocol numberof JXAU20220007.