RT Journal Article
SR Electronic
T1 New SARS-CoV-2 lineages could evade CD8+ T-cells response
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.09.434584
DO 10.1101/2021.03.09.434584
A1 Pretti, Marco Antonio M.
A1 Galvani, Rômulo G.
A1 Farias, Alessandro S
A1 Boroni, Mariana
YR 2021
UL http://biorxiv.org/content/early/2021/03/23/2021.03.09.434584.abstract
AB Background Many SARS-CoV-2 variants of concern have emerged since the Covid-19 outburst, notably the lineages detected in the UK, South Africa, and Brazil. Their increased transmissibility and higher viral load put them in the spotlight. Much has been investigated on the ability of those new variants to evade antibody recognition. However, not enough attention has been given to pre-existing and induced SARS-CoV-2-specific CD8+ T cell responses during the natural course of infection by new lineages.Methods In this work, we investigated the SARS-CoV-2-specific CD8+ T cell epitopes from the main variants of concern and the potential of associated mutations to trigger or hinder CD8+ T-cells response. We also estimated the population’s coverage of these different lineages, considering peptide binding predictions to class I HLA alleles from 29 countries to investigate differences in the fraction of individuals expected to respond to a given epitope set from new and previous lineages.Results We observed a lower populational coverage for 20B/S.484K (P.2 lineage) in contrast to an increased coverage found for 20H/501Y.V2 (B.1.351 Lineage) and 20J/501Y.V3 (P.1 lineage) compared to a reference lineage. Moreover, mutations such as Spike N501Y and Nucleocapsid T205I were predicted to have an overall higher affinity through HLA-I than the reference sequence.Conclusions In summary, the data in this work provided evidence for the existence of potentially immunogenic and conserved epitopes across new SARS-CoV-2 variants, but also highlights the reduced populational’s coverage for the Brazilian lineage P.2, suggesting its potential to evade from CD8+ T-cell responses. Our results also may guide efforts to characterize and validate relevant peptides to trigger CD8+ T-cell responses, and design new universal T-cell-inducing vaccine candidates that minimize detrimental effects of viral diversification and at the same time induce responses to a broad human population.Competing Interest StatementThe authors have declared no competing interest.aaamino acidHLAHuman Leukocyte AntigenIFN-γInterferon gammaIL-2Interleukin-2MERSMiddle east respiratory syndromeNNucleocapsidnsSNVsNon-synonymous single-nucleotide variantsRBDReceptor Binding DomainREFreference lineageSSpikeSARSSevere acute respiratory syndromeSARS-CoV-2Severe acute respiratory syndrome coronavirus 2SBStrong BinderTCRT-cell receptorTNF-ɑTumor necrosis factorVOIvariant of interestWBWeak Binder