Evolution of SARS-CoV-2-specific CD4+ T cell epitopes

Abstract

Vaccination clearly decreases coronavirus disease 2019 (COVID-19) mortality; however, they also impose selection pressure on the virus, which promotes the evolution of immune escape variants. For example, despite the high vaccination level in especially Western countries, the Omicron variant caused millions of breakthrough infections, suggesting that the highly mutated spike protein in the Omicron variant can escape antibody immunity much more efficiently than the other variants of concern (VOCs). In this study, we investigated the resistance/susceptibility of T helper cell responses that are necessary for generating efficient long-lasting antibody immunity, in several VOCs. By predicting T helper cell epitopes on the spike protein for most common HLA-DRB1 alleles worldwide, we found that although most of high frequency HLA-DRB1 alleles have several potential T helper cell epitopes, few alleles like HLA-DRB1 13:01 and 11:01 are not predicted to have any significant T helper cell responses after vaccination. Using these predictions, a population based on realistic human leukocyte antigen-II (HLA-II) frequencies were simulated to visualize the T helper cell immunity on the population level. While a small fraction of this population had alarmingly little predicted CD4 T cell epitopes, the majority had several epitopes that should be enough to generate efficient B cell responses. Moreover, we show that VOC spike mutations hardly affect T helper epitopes and mainly occur in other residues of the spike protein. These results suggest that lack of long-lasting antibody responses is not likely due to loss of T helper cell epitopes in new VOCs.

Phylogenetic Analysis and Codon Usage Bias Reveal the Base of Feline and Canine Chaphamaparvovirus for Cross-Species Transmission

“…These pressures can influence the survival and replication of viral strains, with some variants becoming more successful due to their specific adaptations. The selection pressure drives the process of natural selection, which can result in the emergence of new viral strains with improved fitness in a given environment [ 56 , 57 , 58 , 59 ]. Therefore, the selective pressure on CaChPV and FeChPV warrants attention, and further monitoring of the virus should be intensified to assess its evolutionary status.…”