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

Autor: Maeva Katzmarzyk, Denise Christine Clesle, Joop van den Heuvel, Markus Hoffmann, Henk Garritsen, Stefan Pöhlmann, Henning Jacobsen, Luka Čičin-Šain
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Frontiers in Immunology, Vol 14 (2023)
Druh dokumentu: article
ISSN: 1664-3224
DOI: 10.3389/fimmu.2023.1288794
Popis: IntroductionThe 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.MethodsTo 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.ResultsWe 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.DiscussionThese data might help to predict antigenic features of novel viral variants carrying these mutations and support the development of broad monoclonal antibodies.
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