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.
【초록키워드】 Evolution, SARS-CoV-2, Mutation, adaptive, neutralization, Vaccine design, mutations, Infection, immunodeficiency, peptide, Immunocompromised patient, Epitopes, Region, lymphoma, Impact, Patient, SARS-CoV-2 mutations, mutant, convalescent, epitope, lineages, Donor, Coronavirus-2, chronic infection, CD8 T cell, humoral, acute respiratory syndrome, Recognition, SARS-CoV-2 sequence, circulating, Effect, homoplasy, resulting, identify, affected, reduced, the spike protein, plasma-mediated, 【제목키워드】 Mutation, antibody, SARS-COV-2 infection, B cell, lymphoma, Patient, epitope, CD8 T cell, accumulation,