Systematical assessment of the impact of single spike mutations of SARS-CoV-2 Omicron sub-variants on the neutralization capacity of post-vaccination sera

Maeva Katzmarzyk; Denise Christine Clesle; Joop van den Heuvel; Markus Hoffmann; Henk Garritsen; Stefan Pöhlmann; Henning Jacobsen; Luka Čičin-Šain

doi:10.3389/fimmu.2023.1288794

Systematical assessment of the impact of single spike mutations of SARS-CoV-2 Omicron sub-variants on the neutralization capacity of post-vaccination sera

Front Immunol. 2023 Nov 10:14:1288794. doi: 10.3389/fimmu.2023.1288794. eCollection 2023.

Authors

Maeva Katzmarzyk¹, Denise Christine Clesle¹, Joop van den Heuvel², Markus Hoffmann^{3

4}, Henk Garritsen^{5

6}, Stefan Pöhlmann^{3

4}, Henning Jacobsen^#¹, Luka Čičin-Šain^#^{1

7

8}

Affiliations

¹ Department of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
² Research Group Recombinant Protein Expression, Helmholtz Centre for Infection Research, Braunschweig, Germany.
³ Infection Biology Unit, German Primate Center, Göttingen, Germany.
⁴ Faculty of Biology and Psychology, Georg-August-University Göttingen, Göttingen, Germany.
⁵ Institute for Clinical Transfusion Medicine, Klinikum Braunschweig GmbH, Braunschweig, Germany.
⁶ Fraunhofer Institute for Surface Engineering and Thin Films IST, Braunschweig, Germany.
⁷ German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany.
⁸ Centre for Individualized Infection Medicine (CIIM), Joint Venture of Helmholtz Centre for Infection Research and Medical School Hannover, Braunschweig, Germany.

^# Contributed equally.

Abstract

Introduction: The evolution of novel SARS-CoV-2 variants significantly affects vaccine effectiveness. While these effects can only be studied retrospectively, neutralizing antibody titers are most used as correlates of protection. However, studies assessing neutralizing antibody titers often show heterogeneous data.

Methods: To address this, we investigated assay variance and identified virus infection time and dose as factors affecting assay robustness. We next measured neutralization against Omicron sub-variants in cohorts with hybrid or vaccine induced immunity, identifying a gradient of immune escape potential. To evaluate the effect of individual mutations on this immune escape potential of Omicron variants, we systematically assessed the effect of each individual mutation specific to Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5.

Results: We cloned a library of pseudo-viruses expressing spikes with single point mutations, and subjected it to pooled sera from vaccinated hosts, thereby identifying multiple mutations that independently affect neutralization potency.

Discussion: These data might help to predict antigenic features of novel viral variants carrying these mutations and support the development of broad monoclonal antibodies.

Keywords: COVID-19; SARS-CoV-2; antibody; neutralizing antibodies; omicron; spike protein.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Neutralizing
COVID-19* / prevention & control
Humans
Mutation
Retrospective Studies
SARS-CoV-2* / genetics
Vaccination

Substances

Antibodies, Neutralizing

Supplementary concepts

SARS-CoV-2 variants

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the COVID-19 Research Network Lower Saxony (COFONI) in the Flex-Funds procedure “COFONI-PREMUS” (10FF22) and by the project “Virological and immunological determinants of COVID-19 pathogenesis—lessons to get prepared for future pandemics (KA1-Co-02 “COVIPA”)”, a grant from the Helmholtz Association’s Initiative and Networking Fund. We thank the Peter and Traudl Engelhorn foundation for providing a post-doctoral fellowship to HJ.