tetano
Editor, Senior Moderator
Nat Commun
. 2022 Sep 23;13(1):5586.
doi: 10.1038/s41467-022-32772-5.
Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection
Elham Khatamzas[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Markus H Antwerpen[SUP] #[/SUP][SUP] 4 5 [/SUP], Alexandra Rehn[SUP] 4 5 [/SUP], Alexander Graf[SUP] 6 [/SUP], Johannes Christian Hellmuth[SUP] 7 8 [/SUP], Alexandra Hollaus[SUP] 7 5 [/SUP], Anne-Wiebe Mohr[SUP] 7 5 [/SUP], Erik Gaitzsch[SUP] 7 [/SUP], Tobias Weiglein[SUP] 7 [/SUP], Enrico Georgi[SUP] 4 5 [/SUP], Clemens Scherer[SUP] 8 9 [/SUP], Stephanie-Susanne Stecher[SUP] 10 [/SUP], Stefanie Gruetzner[SUP] 11 [/SUP], Helmut Blum[SUP] 6 [/SUP], Stefan Krebs[SUP] 6 [/SUP], Anna Reischer[SUP] 7 [/SUP], Alexandra Leutbecher[SUP] 7 [/SUP], Marion Subklewe[SUP] 7 [/SUP], Andrea Dick[SUP] 12 [/SUP], Sabine Zange[SUP] 4 5 [/SUP], Philipp Girl[SUP] 4 5 [/SUP], Katharina Müller[SUP] 4 5 [/SUP], Oliver Weigert[SUP] 7 13 [/SUP], Karl-Peter Hopfner[SUP] 14 [/SUP], Hans-Joachim Stemmler[SUP] 7 [/SUP], Michael von Bergwelt-Baildon[SUP] 7 8 13 [/SUP], Oliver T Keppler[SUP] 8 5 15 [/SUP], Roman Wölfel[SUP] 4 5 [/SUP], Maximilian Muenchhoff[SUP] #[/SUP][SUP] 8 5 15 [/SUP], Andreas Moosmann[SUP] #[/SUP][SUP] 7 5 [/SUP]
Affiliations
Abstract
Antibodies 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.
. 2022 Sep 23;13(1):5586.
doi: 10.1038/s41467-022-32772-5.
Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection
Elham Khatamzas[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Markus H Antwerpen[SUP] #[/SUP][SUP] 4 5 [/SUP], Alexandra Rehn[SUP] 4 5 [/SUP], Alexander Graf[SUP] 6 [/SUP], Johannes Christian Hellmuth[SUP] 7 8 [/SUP], Alexandra Hollaus[SUP] 7 5 [/SUP], Anne-Wiebe Mohr[SUP] 7 5 [/SUP], Erik Gaitzsch[SUP] 7 [/SUP], Tobias Weiglein[SUP] 7 [/SUP], Enrico Georgi[SUP] 4 5 [/SUP], Clemens Scherer[SUP] 8 9 [/SUP], Stephanie-Susanne Stecher[SUP] 10 [/SUP], Stefanie Gruetzner[SUP] 11 [/SUP], Helmut Blum[SUP] 6 [/SUP], Stefan Krebs[SUP] 6 [/SUP], Anna Reischer[SUP] 7 [/SUP], Alexandra Leutbecher[SUP] 7 [/SUP], Marion Subklewe[SUP] 7 [/SUP], Andrea Dick[SUP] 12 [/SUP], Sabine Zange[SUP] 4 5 [/SUP], Philipp Girl[SUP] 4 5 [/SUP], Katharina Müller[SUP] 4 5 [/SUP], Oliver Weigert[SUP] 7 13 [/SUP], Karl-Peter Hopfner[SUP] 14 [/SUP], Hans-Joachim Stemmler[SUP] 7 [/SUP], Michael von Bergwelt-Baildon[SUP] 7 8 13 [/SUP], Oliver T Keppler[SUP] 8 5 15 [/SUP], Roman Wölfel[SUP] 4 5 [/SUP], Maximilian Muenchhoff[SUP] #[/SUP][SUP] 8 5 15 [/SUP], Andreas Moosmann[SUP] #[/SUP][SUP] 7 5 [/SUP]
Affiliations
- PMID: 36151076
- PMCID: PMC9508331
- DOI: 10.1038/s41467-022-32772-5
Abstract
Antibodies 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.