Rapid spread of the SARS-CoV-2 JN.1 lineage is associated with increased neutralization evasion
Lu Zhang,
Alexandra Dopfer-Jablonka,
Anne Cossmann,
Metodi V. Stankov,
Luise Graichen,
Anna-Sophie Moldenhauer,
Christina Fichter,
Anupriya Aggarwal,
Stuart G. Turville,
Georg M.N. Behrens,
Stefan Pöhlmann,
Markus Hoffmann
Affiliations
Lu Zhang
Infection Biology Unit, German Primate Center, Göttingen, Germany; Faculty of Biology and Psychology, Georg-August-University Göttingen, Göttingen, Germany
Alexandra Dopfer-Jablonka
Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany; German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Hannover, Germany
Anne Cossmann
Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany
Metodi V. Stankov
Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany
Luise Graichen
Infection Biology Unit, German Primate Center, Göttingen, Germany; Faculty of Biology and Psychology, Georg-August-University Göttingen, Göttingen, Germany
Anna-Sophie Moldenhauer
Infection Biology Unit, German Primate Center, Göttingen, Germany
Christina Fichter
The Kirby Institute, University of New South Wales, Sydney, NSW, Australia
Anupriya Aggarwal
The Kirby Institute, University of New South Wales, Sydney, NSW, Australia
Stuart G. Turville
The Kirby Institute, University of New South Wales, Sydney, NSW, Australia
Georg M.N. Behrens
Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany; German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Hannover, Germany; Center for Individualized Infection Medicine (CiiM), Hannover, Germany
Stefan Pöhlmann
Infection Biology Unit, German Primate Center, Göttingen, Germany; Faculty of Biology and Psychology, Georg-August-University Göttingen, Göttingen, Germany
Markus Hoffmann
Infection Biology Unit, German Primate Center, Göttingen, Germany; Faculty of Biology and Psychology, Georg-August-University Göttingen, Göttingen, Germany; Corresponding author
Summary: In July/August 2023, the highly mutated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.2.86 lineage emerged and its descendant JN.1 is on track to become the dominant SARS-CoV-2 lineage globally. Compared to the spike (S) protein of the parental BA.2.86 lineage, the JN.1 S protein contains one mutation, L455S, which may affect receptor binding and antibody evasion. Here, we performed a virological assessment of the JN.1 lineage employing pseudovirus particles bearing diverse SARS-CoV-2 S proteins. Using this strategy, it was found that S protein mutation L455S confers increased neutralization resistance but reduces ACE2 binding capacity and S protein-driven cell entry efficiency. Altogether, these data suggest that the benefit of increased antibody evasion outweighs the reduced ACE2 binding capacity and further enabled the JN.1 lineage to effectively spread in the human population.
