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Publications

Journal Article Research Support, Non-U.S. Gov't Epublish 7 citations

PubMed: 38022629 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 14:1288794

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

Affiliations

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

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.

MeSH

Sars-Cov-2, Vaccines, Antibodies, Neutralizing, Vaccination, Immune System Diseases, Viruses, Severe Acute Respiratory Syndrome-Related Coronavirus, Mutation

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