Mutations of SARS-CoV-2 variants of concern escaping Spike-specific T cells

Abstract

The amino acid (AA) mutations that characterize the different variants of concern (VOCs), which replaced the ancestral SARS-CoV-2 Wuhan-Hu-1 isolate worldwide, provide biological advantages such as increased infectivity and partial escape from humoral immunity. Here we analyzed the impact of these mutations on vaccination- and infection-induced Spike-specific T cells. We confirmed that, in the majority of infected or vaccinated individuals, different mutations present in a single VOC (Delta) or a combined mosaic of more than 30 AA substitutions and deletions found in Alpha, Beta, Gamma, Delta and Omicron VOCs cause modest alteration in the global Spike-specific T cell response. However, distinct numerically dominant Spike-specific CD4 and CD8 T cells preferentially targeted regions affected by AA mutations and do not recognize the mutated peptides. Importantly, some of these mutations, such as N501Y (present in Alpha, Beta, Gamma, and Omicron) and L452R (present in Delta), known to provide biological advantage to SARS-CoV-2 in terms of infectivity also abolished CD8 T cell recognition. Taken together, our data show that while global mRNA vaccine- and infection-induced Spike-specific T cells largely tolerate the diverse mutations present in VOCs, single Spike-specific T cells might contribute to the natural selection of SARS-CoV-2 variants.

Bioinformatic and Experimental Analysis of T Cell Immune Reactivity to SARS-CoV-2 and its Variants

“…Thus, these data do not support the notion of a selective pressure for mutation of the T cell epitopes at the population level. It is worth noting that while this has been confirmed at the experimental level exvivo, additional unknown factors may influence the expansion of specific T cell clones among the epitope pools considered herein and found to be more affected by viral mutations (Le Bert et al, 2022).…”

COVID-19 and the Path to Immunity

“…Simultaneously, SARS-CoV-2 activates T cells in the first week of infection, and virus-specific memory CD4 + cells and CD8 + T cells reportedly peak within 2 weeks but remain detectable at lower levels for 100 or more days of observation. Grifoni et al 1 and others 5,6 have identified SARS-CoV-2-specific memory CD4 + T cells in up to 100% and CD8 + T cells in approximately 70% of patients recovering from COVID-19. Although severe COVID-19 is characterized by high-viral titers, dysregulated innate inflammatory cytokine and chemokine responses and prolonged lymphopenia, antibody-dependent enhancement or dominant CD4 + T H 2-type cytokines (eg, IL-4, IL-5, IL-13) do not appear to contribute to acute COVID-19 severity.The magnitude of the antibody and T-cell responses can differ and be discordant among individuals and is influenced by disease severity (asymptomatic, mild, moderate, or severe).…”

“…SARS-CoV-2-specific CD4 + and CD8 + memory T cells are also generated in asymptomatic to severe disease, 1,5,6 which exhibit cytotoxic activities and express antiviral cytokines, features that may control viral replication and prevent recurrent severe infections. Analysis of CD4 + T cell responses indicate a predominant polarization to a T H 1 type, 1 although the roles T H 17 and T H 2 cytokines and cytotoxic T cells have in patients with COVID-19 acute respiratory distress syndrome needs greater clarity.…”

“…Substantial data now demonstrate the presence of preexisting T-cell immunity to SARS-CoV-2 in blood donors either prior to the COVID-19 pandemic or more recently among those without infection. 1,5,6 Memory CD4 + T cells are found in higher frequencies than are CD8 + T cells, and these likely represent responses induced by previous infection with other human endemic betacoronaviruses known to cause the common cold. Such T cells can recognize known or predicted epitopes 1 within the nucleocapsid (N protein) and spike structural proteins as well as the nonstructural proteins (NSPs), NSP7 and NSP13.…”

Dynamics of formation of anti- bodies to SARS-CoV-2 after coronavirus infection in children

“…Иммунный ответ против SARS CoV 2 иг рает решающую роль в определении клини ческого исхода как у взрослых, так и у детей [5]. Иммунитет к SARS CoV 2, вызванный ес тественной инфекцией, вероятно, опосредо ван комбинацией гуморального и клеточно го иммунитета [6]. В исследовании, сравни вающем детей и взрослых, выявили разные иммунные профили при коронавирусной инфекции, коррелирующие с менее тяжелы ми исходами у детей [7].…”