

There were no significant differences, regarding the levels of IgG antibodies specific for RBD-Wuhan (Table S4: Median OD C1-C20: 0.385 Median OD D1-D10: 0.453 Median OD T1-T10: 2.339) and RBD-Delta (Table S4: Median OD C1-C20: 0.379 Median OD D1-D10: 0.509 Median OD T1-T10: 2.470) (Table S4, Median reduction in binding comparing RBD-Wuhan with RBD-Delta: 4.3%), whereas RBD-Omicron-specific IgG levels (Table S4: Median OD C1-C20: 0.073 Median OD D1-D10: 0.128 Median OD T1-T10: 0.836) were significantly lower than those specific for RBD-Wuhan (Table S4, Median reduction of binding: 81.2%) and for RBD-Delta in the convalescent patients and vaccinated subjects (Figure 1A-C Table S4). Sera from convalescent patients had been obtained from April to July 2020, 3 43–92 days (median 57.5 days) after the PCR confirmation of SARS-CoV-2 infection, sera from subjects vaccinated two times had been collected 26–31 days (median 27.5 days), and samples from subjects vaccinated three times were collected 23–40 days (median 28 days) after the last vaccination, respectively (Tables S2 and S3). Furthermore, we studied the ability of antibodies in these sera to inhibit the binding of RBD-Wuhan, RBD-Delta, and RBD-Omicron to ACE2 using the RBD-ACE2 molecular interaction assay described by Gattinger et al. Here, we compared the IgG recognition of RBD from the original Wuhan strain and recent variants of concern Delta (Pango B.1.617.2) and Omicron (Pango B.1.1.529) (Table S1) using sera from a random sample of adult COVID-19 convalescent patients (Table S2: C1-C20) and a random sample of adult subjects vaccinated two times (Table S3: D1-D10) or three times (Table S3: T1-T10) with a registered vector- (i.e., Vaxzevria) and/or mRNA-based vaccine (i.e., Comirnaty) (Figures 1 and 2 Table S4). 3, 4 The ability of RBD-specific antibodies to prevent RBD binding to ACE2 can be measured with surrogate molecular interaction assays, 5 which mimic classical virus-neutralization tests 3 and can therefore be quickly adapted to newly emerging SARS-CoV-2 variants of concern by using RBDs from the corresponding virus variants. Antibodies directed to RBD are critically important for virus-neutralization because the RBD-ACE2 interaction represents the port of entry for the virus into cells leading to its replication in the host and to the consecutive spreading in the population. In particular, Omicron has significantly more amino acid mutations in the SARS-CoV-2 receptor-binding domain (RBD), which binds to the ACE2 receptor on human cells, as compared with previous SARS-CoV-2 variants 2 (Table S1).

The recently described variant of concern (VOC) Omicron, which has emerged in South Africa in November 2021, is spreading in the meantime rapidly all over the world and has become a matter of great concern because it shows more changes in the SARS-CoV-2 genome that may affect immunity as compared with earlier variants 1 (Supplemental references S6–S9). However, the immunity to SARS-CoV-2 which has been established so far is challenged by the appearance of SARS-CoV-2-variants which may escape cellular (Supplemental reference S4) and antibody-dependent immunity (Supplemental reference S5). Both factors certainly contribute to the fact, that although numbers of worldwide SARS-CoV-2 infections end of 2021 were more than double as high as in the end of 2020, the number of COVID-19-associated deaths has dropped to approximately 50% at the same time ( ). Furthermore, mass production and global application of COVID-19 vaccines have begun (Supplemental reference S3).

As of today (February 14, 2022), more than 410 million persons ( ) have reportedly been infected by SARS-CoV-2.
