Insufficient epitope-specific T cell clones are responsible for impaired cellular immunity to inactivated SARS-CoV-2 vaccine in older adults

Abstract

Aging is a critical risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine efficacy. The immune responses to inactivated vaccine for older adults, and the underlying mechanisms of potential differences to young adults, are still unclear. Here we show that neutralizing antibody production by older adults took a longer time to reach similar levels in young adults after inactivated SARS-CoV-2 vaccination. We screened SARS-CoV-2 variant strains for epitopes that stimulate specific CD8 T cell response, and older adults exhibited weaker CD8 T-cell-mediated responses to these epitopes. Comparison of lymphocyte transcriptomes from pre-vaccinated and post-vaccinated donors suggested that the older adults had impaired antigen processing and presentation capability. Single-cell sequencing revealed that older adults had less T cell clone expansion specific to SARS-CoV-2, likely due to inadequate immune receptor repertoire size and diversity. Our study provides mechanistic insights for weaker response to inactivated vaccine by older adults and suggests the need for further vaccination optimization for the old population.

Global analysis of HLA-A2 restricted MAGE-A3 tumor antigen epitopes and corresponding TCRs in non-small cell lung cancer

“…The MAGE-A3-Mp4 epitope-specific CD8+ T cells were sorted after tetramer staining ( Figure S3 A-C) and used for paralleled single-cell RNA-seq and TCR V(D)J sequencing. Healthy donors were used here for a more comprehensive and unbiased profiling of CD8+ T cells after encountering the MAGE-A3 antigens 28 . In total, we produced high-quality scRNA-seq and scTCR-seq data from 5,891 CD8+ T cells with paired TCR chains potentially specific to MAGE-A3-Mp4 epitope.…”

“…T2 cells (0.2×10 6 /well) were seeded into 96-well plates and incubated with 20 µM peptides at 37 °C for 4 hours. DMSO was set as blank control, the HLA-A2 restricted Influenza A (flu) M1 peptide (M58-66 GILGFVFTL) was set as positive control and HLA-A11 restricted EBNA3B (EBV) virus peptide (E416-424 IVTDFSVIK) was set as negative control [26][27][28]. Cells were stained with anti-HLA-A2 antibody (BioLegend, Cat#343305, US) and acquired using flow cytometer FACS Canto (BD).…”

“…Cluster 0, 2, 4, 5, 7, 9 ,10 and 13 were annotated as effector CD8+ T cells according to the reported markers (e.g., IFNG, GZMB, NKG7, CST7 and GNLY) [37][38][39]. Lastly, cluster 3, 11, 12 and 14 featured with high expression of RRM2, YTMS, PCNA and CCNB2, which are related to cell proliferation and cell cycle [28], were named as cycling CD8+ T cells (Figure 4A-B). Re-analysis of the scRNA-seq of two HLA-A2 healthy young adults from our previous study [40] showed that the CD8+ T cells without stimulation mainly included naïve, effector, memory and other CD8+ T cells (Figure S5A-B), of which naïve CD8+ T cells accounted for majority (50.9%) (Figure S5C).…”

Single-cell transcriptomics identifies adipose tissue CD271+ progenitors for enhanced angiogenesis in limb ischemia

“… 24 GEO: GSE184937 scRNAseq Human Umbilical Cord Blood Xiao et al. 68 GEO: GSE157007 scRNAseq Human Umbilical Cord Blood Moison et al. 69 GEO: GSE153370 RNAseq Human Adipose, Limb, and Skeletal Muscle Genotype-Tissue Expression (GTEx) Project gtexportal.org; dbGaP Accession phs000424.v8.p2 RNAseq Human Limb Muscle Ryan et al.…”

Meeting Summary of The NYO3 5th NO-Age/AD Meeting and the 1st Norway–UK Joint Meeting on Aging and Dementia: Recent Progress on the Mechanisms and Interventional Strategies

“…By using single-cell RNA and TCR sequencing of human blood samples across the lifespan, they show an age-dependent accumulation of transcriptome heterogeneity and variability in immune cells ( 44 ). Additionally, he explored the impact of aging on SARS-CoV-2 vaccine efficacy, noting delayed antibody production and weaker T-cell responses in older adults ( 45 ). The findings underscore the importance of understanding aging-related immune dynamics for optimizing vaccinations in the older population.…”