• Maren Schubert, Federico Bertoglio, Stephan Steinke, Philip Alexander Heine, Mario Alberto Ynga-Durand, Henrike Maass, Josè Camilla Sammartino, Irene Cassaniti, Fanglei Zuo, Likun Du, Janin Korn, Marko Milošević, Esther Veronika Wenzel, Fran Krstanović, Saskia Polten, Marina Pribanić-Matešić, Ilija Brizić, Fausto Baldanti, Lennart Hammarström, Stefan Dübel, Alan Šustić, Harold Marcotte, Monika Strengert, Alen Protić, Antonio Piralla, Qiang Pan-Hammarström, Luka Čičin-Šain, and Michael Hust.
• Technische Universität Braunschweig, Institut für Biochemie, Biotechnologie und Bioinformatik, Abteilung Biotechnologie, Spielmannstr. 7, 38106, Braunschweig, Germany.
• Bmc Med. 2022 Mar 3; 20 (1): 102.

BackgroundThe COVID-19 pandemic is caused by the betacoronavirus SARS-CoV-2. In November 2021, the Omicron variant was discovered and immediately classified as a variant of concern (VOC), since it shows substantially more mutations in the spike protein than any previous variant, especially in the receptor-binding domain (RBD). We analyzed the binding of the Omicron RBD to the human angiotensin-converting enzyme-2 receptor (ACE2) and the ability of human sera from COVID-19 patients or vaccinees in comparison to Wuhan, Beta, or Delta RBD variants.MethodsAll RBDs were produced in insect cells. RBD binding to ACE2 was analyzed by ELISA and microscale thermophoresis (MST). Similarly, sera from 27 COVID-19 patients, 81 vaccinated individuals, and 34 booster recipients were titrated by ELISA on RBDs from the original Wuhan strain, Beta, Delta, and Omicron VOCs. In addition, the neutralization efficacy of authentic SARS-CoV-2 wild type (D614G), Delta, and Omicron by sera from 2× or 3× BNT162b2-vaccinated persons was analyzed.ResultsSurprisingly, the Omicron RBD showed a somewhat weaker binding to ACE2 compared to Beta and Delta, arguing that improved ACE2 binding is not a likely driver of Omicron evolution. Serum antibody titers were significantly lower against Omicron RBD compared to the original Wuhan strain. A 2.6× reduction in Omicron RBD binding was observed for serum of 2× BNT162b2-vaccinated persons. Neutralization of Omicron SARS-CoV-2 was completely diminished in our setup.ConclusionThese results indicate an immune escape focused on neutralizing antibodies. Nevertheless, a boost vaccination increased the level of anti-RBD antibodies against Omicron, and neutralization of authentic Omicron SARS-CoV-2 was at least partially restored. This study adds evidence that current vaccination protocols may be less efficient against the Omicron variant.© 2022. The Author(s).

15 keywords...

hide…