Unknown,Transcriptomics,Genomics,Proteomics

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Single cell RNA sequencing of migratory dendritic cells after intranasal adjuvant/tolerogen administration

ABSTRACT: We compared migratory DCs in draining mediastinal lymph node after intranasal administration of different vaccine adjuvants based on CTA1 subunit of cholera toxin. The goal was to determine different characteristics of dendritic cells subsets after pro-inflammatory vs tolerogenic adjuvant. We had 3 groups: CTA1-DD (pro- inflammatory), CTA1(R7K)-DD (tolerogenic) and PBS to define DC which migrate to LN. All vaccine constructs included 3Ea peptide to allow for sorting of DC which took up the vaccine.

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Mus musculus

SUBMITTER: Davide Angeletti

PROVIDER: E-MTAB-12942 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Next-generation T-cell-directed vaccines for COVID-19 aim to induce durable T-cell immunity against circulating and future hypermutated SARS-CoV-2 variants. Mass Spectrometry (MS)based immunopeptidomics holds promise for guiding vaccine design, but computational challenges impede the precise and unbiased identification of conserved T-cell epitopes crucial for vaccines against rapidly mutating viruses. We introduce a computational framework and analysis platform integrating a novel machine learning algorithm, immunopeptidomics, intra-host data, epitope immunogenicity, and geo-temporal CD8+ T-cell epitope conservation analyses. Central to our approach is MHCvalidator, a novel artificial neural network algorithm enhancing MS-based immunopeptidomics sensitivity by modeling antigen presentation and sequence features. MHCvalidator identified a novel nonconventional SARS-CoV-2 T-cell epitope presented by B7 supertype molecules, originating from a +1-frameshift in a truncated Spike (S) antigen, supported by ribo-seq data. Intra-host analysis of SARS-CoV-2 proteomes from ~100,000 COVID-19 patients revealed a prevalent S antigen truncation in ~51% of cases, exposing a rich source of frameshifted viral antigens. Our framework includes EpiTrack, a new computational pipeline tracking global mutational dynamics of MHCvalidator-identified SARS-CoV-2 CD8+ epitopes from vaccine BNT162b4. While most vaccine-encoded CD8+ epitopes exhibit global conservation from January 2020 to October 2023, a highly immunodominant A*01-associated epitope, especially in hospitalized patients, undergoes substantial mutations in Delta and Omicron variants. Our approach unveils unprecedented SARS-CoV-2 T-cell epitopes, elucidates novel antigenic features, and underscores mutational dynamics of vaccine-relevant epitopes. The analysis platform is applicable to any viruses, and underscores the need for continual vigilance in T-cell vaccine development against the evolving landscape of hypermutating SARS-CoV-2 variants.

Dataset Information

Single cell RNA sequencing of migratory dendritic cells after intranasal adjuvant/tolerogen administration

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