The Omicron variant of SARS-CoV-2 appears to be spreading faster than any previous variant and may soon dominate globally. Infection with SARS-CoV-2 and vaccination leads to the production of antibodies that strongly contribute to protection against severe disease. In addition, combinations of antibodies produced by biotechnology approaches are being used to treat COVID-19. The spike protein of SARS-CoV-2 facilitates viral entry into cells and constitutes the central target for antibodies that inhibit (neutralize) the virus. Therefore, it is important to determine whether the Omicron spike is inhibited by antibodies induced upon vaccination or infection or currently used for COVID-19 treatment. The researchers investigated these questions using non-hazardous virus-like particles that carry the Omicron spike and are well suited for analysis of virus entry and its inhibition.
Currently, combinations of the antibodies Casirivimab and Imdevimab, and Etesevimab and Bamlanivimab are used to treat COVID-19. However, the team showed that these antibodies are largely ineffective against the Omicron spike. Only one antibody, Sotrovimab, inhibited the Omicron spike. “Our cell culture studies suggest that most antibodies currently available for COVID-19 therapy will be ineffective against Omicron. Sotrovimab is an exception and could become an important treatment option for Omicron-infected patients,” concluded first author Markus Hoffmann.
The researchers further investigated whether patients infected in Germany during the first wave of the pandemic had produced antibodies that protect against the Omicron variant. While the antibodies inhibited the spike of the virus responsible for the first wave, they had little effect against the Omicron spike. Therefore, it can be assumed that these individuals do not have robust immune protection against the Omicron variant, although an inhibition by T cells, which are also produced during infection, remains to be analyzed.
Antibodies produced after two immunizations with the BioNTech-Pfizer vaccine also inhibited the Omicron spike significantly less efficiently than the spike proteins of other variants. A better protective effect was observed after three immunizations with BioNTech-Pfizer and after heterologous immunization with Oxford-AstraZeneca/BioNTech-Pfizer. These results indicate that dual immunization with BioNTech-Pfizer may protect less efficiently against the Omicron variant as compared to the Delta variant. In contrast, triple immunization with BioNTech-Pfizer (booster) and cross-vaccination with Oxford-AstraZeneca/BioNTech-Pfizer could establish stronger protection.
“Our results indicate that antibody therapies for COVID-19 need to be adapted to the Omicron variant. Adaptation of the BioNTech-Pfizer vaccine should also be considered. In contrast, triple immunization with BioNTech-Pfizer (booster) and cross-vaccination with Oxford-AstraZeneca