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.
| Item Type: | Journal article |
|---|---|
| Faculties: | Medicine > Medical Center of the University of Munich > Medical Clinic and Outpatient Clinic III (Oncology) |
| Subjects: | 600 Technology > 610 Medicine and health |
| URN: | urn:nbn:de:bvb:19-epub-104524-3 |
| ISSN: | 2041-1723 |
| Language: | English |
| Item ID: | 104524 |
| Date Deposited: | 13. Jul 2023, 13:41 |
| Last Modified: | 04. Jan 2024, 12:00 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892 |
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