Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection
2022; Nature Portfolio; Volume: 13; Issue: 1 Linguagem: Inglês
10.1038/s41467-022-32772-5
ISSN2041-1723
AutoresElham Khatamzas, Markus Antwerpen, Alexandra Rehn, Alexander Graf, Johannes C. Hellmuth, Alexandra Hollaus, Anne‐Wiebe Mohr, Erik Gaitzsch, Tobias Weiglein, Enrico Georgi, Clemens Scherer, Stephanie-Susanne Stecher, Stefanie Gruetzner, Helmut Blum, Stefan Krebs, Anna Reischer, Alexandra Leutbecher, Marion Subklewe, Andrea Dick, Sabine Zange, Philipp Girl, Katharina Müller, Oliver Weigert, Karl‐Peter Hopfner, Hans‐Joachim Stemmler, Michael von Bergwelt‐Baildon, Oliver T. Keppler, Roman Wölfel, Maximilian Muenchhoff, Andreas Moosmann,
Tópico(s)T-cell and B-cell Immunology
ResumoAntibodies against the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can drive adaptive evolution in immunocompromised patients with chronic infection. Here we longitudinally analyze SARS-CoV-2 sequences in a B cell-depleted, lymphoma patient with chronic, ultimately fatal infection, and identify three mutations in the spike protein that dampen convalescent plasma-mediated neutralization of SARS-CoV-2. Additionally, four mutations emerge in non-spike regions encoding three CD8 T cell epitopes, including one nucleoprotein epitope affected by two mutations. Recognition of each mutant peptide by CD8 T cells from convalescent donors is reduced compared to its ancestral peptide, with additive effects resulting from double mutations. Querying public SARS-CoV-2 sequences shows that these mutations have independently emerged as homoplasies in circulating lineages. Our data thus suggest that potential impacts of CD8 T cells on SARS-CoV-2 mutations, at least in those with humoral immunodeficiency, warrant further investigation to inform on vaccine design.
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