Cross-Reactivity of IgG Antibodies and Virus Neutralization in mRNA-Vaccinated People Against Wild-Type SARS-CoV-2 and the Five Most Common SARS-CoV-2 Variants of Concern

Abstract

The rapid development, approval, and production of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in less than 1 year after the first reports of a new infectious disease was a real game changer, providing 80%–90% efficacy in preventing severe etiopathologies of the coronavirus disease 2019 (COVID-19). These vaccines induce an immune response against the SARS-CoV-2 spike (S) protein located on the surface of the virus particle. Antibodies (Abs) recognizing the S-protein can inhibit binding of the virus via the S-protein to the angiotensin-converting enzyme-2 (ACE-2) receptor expressed on different human cells, especially when these Abs bind to the interaction site, the so-called receptor-binding domain (RBD). We have expressed the RBDs of wild-type SARS-CoV-2 and five variants of concern (VOCs) to test the immune response in people before vaccination with mRNA vaccines BNT162b2 and mRNA-1273 and after up to three vaccinations using in-house ELISA and inhibition assays. The methods of both assays are provided. Both vaccines initiated similarly high IgG titers after two vaccinations against the wild-type and even two VOC-RBDs (alpha and delta) and strongly inhibited the corresponding RBD-ACE-2 binding. The IgG titers and inhibition of ACE-2 binding were lower for beta and gamma RBDs and much lower for omicron RBD. The third vaccination after 6 months strongly increased both the IgG titers and the neutralizing effect against all variants, especially for omicron, leading to 63% ± 13% neutralization potential. Importantly, neutralization linearly increased with the IgG titers.

Shared 6mer Peptides of Human and Omicron (21K and 21L) at SARS-CoV-2 Mutation Sites

“…On a similar basis, there is a need to investigate the possible changes in molecular mimicry-based autoimmunity risk. In accordance, cross-reactivities of Ig antibodies and virus neutralization in mRNA vaccinated people were reported [ 55 ], implying the need for more studies. Consequently, the possible molecular mimicry-based autoimmunity risk of the Omicron Nextstrain clades 21K and 21L was investigated here.…”

Evaluation of S- and M-Proteins Expressed in Escherichia coli and HEK Cells for Serological Detection of Antibodies in Response to SARS-CoV-2 Infections and mRNA-Based Vaccinations

“…The proteins were purified by IMAC using a HisTrap TM HP (GE Healthcare) column (RBD-protein) and StrepTactin affinity chromatography using a StrepTrap TM HP (Cytiva, Marlborough, MA, USA) column (S1-protein, M-protein) following the manufacturers' guidelines. Size-exclusion chromatography (SEC) followed for the proteins (RBD, S1), as recently reported [21].…”

“…More importantly, the RBD-protein represents the ACE-2 binding site and thus antibodies recognizing this protein in ELISA will probably also inhibit RBD-ACE-2 interactions. Thus, the ELISA will also indicate neutralizing effects, although advanced neutralization assays will provide more reliable data [21,35,36].…”

“…However, the value of this sensitivity is limited by the low specificity of only 84.0%. An important application of the RBD-protein ELISA is the investigation of the vaccination status, because most antibodies recognizing the RBD will most likely reduce or abolish the binding to ACE-2, as confirmed by neutralizing assays [21]. The current study focused on mRNA vaccines BNT162b2 and mRNA-1273 in different combinations and monitoring the immune response for up to three vaccinations (Table S2).…”

Progress in Biosensors for the Point-of-Care Diagnosis of COVID-19

“…The exact diagnosis can be based on various techniques and instruments, including the techniques locating damaged tissues such as tomography and sonography [ 29 , 30 , 31 ] and molecular biology methods such as polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) in their reverse transcriptase [ 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. Immunochemical methods such as enzyme-linked immunosorbent assay (ELISA) for the detection of specific antibodies or the presence of the COVID antigen can also be used [ 39 , 40 , 41 , 42 ]. The mentioned methods generally exert good accuracy and reliability.…”