2021-12-13

Antibodies of vaccinated or hospitalized COVID-19 individuals still recognize the Omicron variant of SARS-CoV-2

TU Braunschweig and HZI analyzed serum samples from vaccinated individuals with new corona variant

The rapid expansion of the Omicron variant has taken the international medical and scientific community by surprise. After infection or vaccination against the coronavirus, our bodies produce antibodies that play a key role in protecting us against COVID-19. While early reports indicate that numerous mutations on the virus surface of the Omicron variant may allow the virus to escape this immune recognition, it is unclear if the mutations improve binding to cell surface receptors and thus facilitate the infection.

Structural model of the spike protein of SARS-CoV-2.Structural model of the spike protein of SARS-CoV-2. The sites where the structure of omicron shows changes are marked in red. The structural model is based on PDB file 6LZG (Figure: Stefan Dübel, TU Braunschweig). © Stefan Dübel/TU BraunschweigThe SARS-CoV-2 coronavirus carries different surface proteins, where Spike is the most prominent example and a crucial component of vaccine formulations. The Spike of the new Omicron variant has been investigated by a team of researchers from the Braunschweig University of Technology together with partners from the EU consortium ATAC (Antibody Therapy Against Corona), the Helmholtz Centre for Infection Research (HZI) and the University of Rijeka in a preprint-study that has not yet been peer-reviewed. The consortium tested the biological characteristic of the Spike receptor binding domain. "Surprisingly, we see that the Omicron variant of the spike protein binds the cell surface receptor less efficiently than the currently circulating virus. On the other hand, both COVID patients and vaccinated persons have reduced antibody responses against Omicron. This suggest that 15 mutations present in the Omicron RBD are there rather to allow the virus to escape recognition but not to infect cells more efficiently." says Prof Luka Cicin-Sain from Helmholtz Centre for Infection Research.

Production of these proteins in the lab allows tests of blood serum to assess the immune response or of their ability to bind to proteins on host cells. "We were already able to produce viral proteins very quickly in insect cells for the development of our COVID-19 drug and for testing patient samples in February 2020, thanks to a new production system I developed," said Dr Maren Schubert from the Department of Biotechnology at TU Braunschweig. Her colleague Dr Federico Bertoglio adds, " The possibility for very rapid biotechnological production of SARS-CoV-2 proteins was also essential for this study."

The quantification of immune responses against coronavirus-2 (SARS-CoV-2) after vaccination is essential to optimally adapt vaccination strategies.  For the ATAC study, 64 serum samples were analyzed. The binding strength of the antibodies against the Omicron variant was compared with the binding strength against the current variants Wuhan, Beta and Delta. The results show that antibodies of the immunoglobulin G (IgG) type against Omicron were detectable in the blood of patients hospitalized for COVID-19 as well as in samples collected after vaccination. However, there was decreased binding compared to the original Wuhan virus or the Delta variants, even after the booster vaccination. This suggests that partial protection against SARS-CoV-2 is provided, but that novel vaccine formulations may become necessary, in accordance with neutralizing effects of antibodies against live viruses, as seen by other labs.

"In the future, our experience will also allow us to develop diagnostic tests and drugs against infectious diseases even faster, and we have also benefited greatly from the many international collaborations we have established in the field of infectious diseases research.", comments Prof Michael Hust, head of the ATAC team at TU Braunschweig:  and adds "The mutations in the Omicron variant are very dynamic and represent only a snapshot. We will also test other Omicron variants". Prof Stefan Dübel, head of the Department of Biotechnology at the Technical University of Braunschweig, added: "In particular, we would like to contribute with our laboratory tools to the planned internationally coordinated defense strategy against future pandemics."

The new preliminary study also builds on findings from the research team in Braunschweig on the immune response in unvaccinated COVID-19 patients from 2020 and the development of a drug against COVID-19. Participants in the new study included the Department of Biotechnology at Braunschweig University of Technology and the Helmholtz Centre for Infection Research in Braunschweig, Germany, as well as the Karolinska Institute in Stockholm, Sweden; Institute for Research in Biomedicine (IRB) in Bellinzona, Switzerland; Joint Research Center (JRC) of the European Commission in Ispra, Italy; Policlinico San Matteo in Pavia, Italy, and the University of Rijeka, Croatia.

Original publication (preprint):

Maren Schubert*, Federico Bertoglio*, Stephan Steinke, Philip Alexander Heine, Mario Alberto Ynga-Durand, Fanglei Zuo, Likun Du, Janin Korn, Marko Milošević, Esther Veronika Wenzel, Henrike Maass, Fran Krstanović, Saskia Polten, Marina Pribanić-Matešić, Ilija Brizić, Antonio Piralla, Fausto Baldanti, Lennart Hammarström, Stefan Dübel, Alan Šustić, Harold Marcotte, Monika Strengert, Alen Protić, Qiang Pan Hammarström#, Luka Čičin-Šain#, Michael Hust#: Human serum from SARS-CoV-2 vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant in comparison to the original Wuhan strain and the Beta and Delta variants. medRxiv. December 2021. DOI: 10.1101/2021.12.10.21267523 (* contributed equally, #corresponding authors)

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