Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection.
Nat Commun
; 13(1): 5586, 2022 09 23.
Article
in English
| MEDLINE | ID: covidwho-2042319
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Vaccines
/
COVID-19
/
Lymphoma
Type of study:
Case report
Topics:
Vaccines
Limits:
Humans
Language:
English
Journal:
Nat Commun
Journal subject:
Biology
/
Science
Year:
2022
Document Type:
Article
Affiliation country:
S41467-022-32772-5
Similar
MEDLINE
...
LILACS
LIS