Omicron, the therapy and protection against Coronavirus disease 2019 (COVID-19) are based on antibodies that neutralize SARS-CoV-2. As a result, SARS-CoV-2 variants with antibody evasion jeopardise critical COVID-19 prevention and treatment strategies.

Because of the significant number of mutations in the spike (S) protein of the Omicron variant of concern, the neutralization susceptibility of the SARS-CoV-2 Omicron BA.1 sublineage following COVID-19 or vaccination is poor (VOC). As a result, Omicron infections have a lower vaccination efficacy and a higher re-infection rate than the other SARS-CoV-2 variants.

Notably, the newly emerged Omicron sublineages BA.2 and BA.1.1 have quickly emerged as the dominant circulating SARS-CoV-2 variants.

Concerning the research
Polyclonal serum activity against the SARS-CoV-2 Omicron BA.2, BA.1, and BA.1.1 sublineages was determined in 50 COVID-19 vaccinated or convalescent individuals in the current study. The authors also used 163 antibodies to determine the antibody sensitivities of the SARS-CoV-2 variants at the monoclonal level.

Before enrolling in the study, all volunteers provided written informed consent. Between April and May 2020, 20 serum samples from COVID-19 recovered patients were obtained from the University Hospital Cologne.

Omicron variant spike protein shows significantly weaker membrane fusion  activity than other variants

People who had a history of polymerase chain reaction (PCR)-confirmed COVID-19 were enrolled in the current study within eight weeks of SARS-CoV-2 diagnosis or symptom onset and were followed up on a long-term basis to assess long-term immunity to the virus. The individuals were most likely infected with SARS-CoV-2 Wu01-like strains ancestors.

In addition, 30 serum samples were collected from SARS-CoV-2 vaccinated health care workers. This study included all health-care workers who received COVID-19 vaccinations at the Charité – Universitätsmedizin in Berlin, Germany, regardless of their health status.

The SeraSpot immunoassay based on the anti-SARS-CoV-2 immunoglobulin G (IgG) microarray was used to screen all serum samples for antibodies against the SARS-CoV-2 nucleocapsid (N) protein.

The vaccination cohort did not include samples from people who had previously been infected with SARS-CoV-2, had a SARS-CoV-2-positive nucleic acid amplification test, or had detectable anti-N antibodies. Furthermore, both the infection and vaccination groups were vaccinated with the COVID-19 messenger ribonucleic acid (mRNA) BNT162b2 vaccine nine and 14 months after receiving two BNT162b2 doses and being infected with SARS-CoV-2, respectively.

Following centrifugation, serum samples were obtained and stored at -80°C until analysis. Using lentivirus-based pseudovirus experiments, the neutralising capacity of serum samples against the three Omicron sublineages was investigated. As a reference, the ancestral SARS-CoV-2 Wu01 strain was used.

Notably, most Wu01-neutralizing antibodies lost their ability to neutralise Omicron sublineages. While the majority of BA.1-neutralizing antibodies, such as R568-1G9 and R207-2F11, were also active against BA.2 and BA.1.1, a subset of antibodies with Omicron-neutralizing activity specific to BA.2 suggests sublineage antigenicity distinctions.

Furthermore, the higher prevalence of BA.2-neutralizing antibodies versus BA.1-neutralizing antibodies among the analysed antibodies suggests that the BA.2 S protein has fewer resistance-related characteristics.

The majority of the 18 monoclonal antibodies (mAbs) tested were either in development or in clinical use and neutralised the SARS-COV-2 Wu01 strain. Sotrovimab, on the other hand, had a less potent effect against Wu01. Most mAbs in clinical use or development, on the other hand, were resistant to the common Omicron BA.2, BA.1.1, and BA.1 sublineages. However, Omicron sensitivity to these antibodies may vary significantly at the sublineage level.

The DZIF-10c mAb, for example, neutralised the Omicron BA.1 sublineage but not the BA.1.1 sublineage. Cilgavimab had significant neutralising activity against BA.2 that was comparable to Wu01 neutralising levels and was >800-times more effective than BA.1.1 and BA.1. Bebtelovimab had the strongest neutralising capacity against the three Omicron sublineages of all the mAbs tested. Thus, when selecting mAbs for the treatment or prophylaxis of Omicron infections, sublineage identification or epidemiology should be taken into account.

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