SARS-CoV-2 Omicron (BA.1 and BA.2) specific novel CD8+ and CD4+ T cell epitopes targeting spike protein

Parn, Simone; Savsani, Kush; Dakshanamurthy, Sivanesan

doi:10.1016/j.immuno.2022.100020

Cited by 4 publications

(1 citation statement)

References 63 publications

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“…This study focuses on the development of design protocol to create personalized peptide vaccines with application to PDAC. The protocol identifies genetic variants using RNAseq analysis and designs a personalized peptide vaccine using a vaccine development protocol and omics pipeline previously developed by our group [21][22][23][24][25][26][27][28][29].…”

Section: Preprintsmentioning

confidence: 99%

Novel Methodology for the Design of Personalized Cancer Vaccine Targeting Neoantigens: Application to Pancreatic Ductal Adenocarcinoma.

Savsani,

Dakshanamurthy

2024

Preprint

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Personalized cancer vaccines have emerged as a promising avenue for cancer treatment or prevention strategies. This approach targets the specific genetic alterations in individual patient’s tumors, offering a more personalized and effective treatment option. Previous studies have shown that generalized peptide vaccines targeting a limited scope of gene mutations are ineffective, emphasizing the need for personalized approaches. While studies have explored personalized mRNA vaccines, personalized peptide vaccines have not yet been studied in this context. Pancreatic ductal adenocarcinoma (PDAC) remains challenging in oncology, necessitating innovative therapeutic strategies. In this study, we developed a personalized peptide vaccine design methodology, employing RNA sequencing (RNAseq) to identify prevalent gene mutations underlying PDAC development in a specific patient solid tumor tissue. We performed RNAseq analysis for trimming adapters, read alignment, and somatic variant calling. We also developed a Python program, called GeneFinder, which validates the alignment of the RNAseq analysis. The Python program is freely available to download. Using chromosome number and locus data, GeneFinder identifies the target gene along the UCSC hg38 reference set. Based on the gene mutation data, we developed a personalized PDAC cancer vaccine that targets 100 highly prevalent gene mutations in the individual patient. We predicted peptide-MHC binding affinity, immunogenicity, antigenicity, allergenicity, and toxicity for each epitope. Then, we selected the top 50 and 100 epitopes based on our previously published vaccine design methodology. Finally, we generated pMHC-TCR 3D molecular model complex structures which are freely available fo download. The designed personalized cancer vaccine contains epitopes commonly found in PDAC solid tumor tissue. Our personalized vaccine was composed of neoantigens, allowing for a more precise and targeted immune response against cancer cells. Additionally, we identified mutated genes which were also found in the reference study where we obtained the sequencing data, thus validating our vaccine design methodology. This is the first study designing a personalized peptide vaccine using human patient data to identify gene mutations associated with the specific tumor of interest.

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Section: Preprintsmentioning

confidence: 99%

Novel Methodology for the Design of Personalized Cancer Vaccine Targeting Neoantigens: Application to Pancreatic Ductal Adenocarcinoma.

Savsani,

Dakshanamurthy

2024

Preprint

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Correlative CD4 and CD8 T-cell immunodominance in humans and mice: Implications for preclinical testing

Neto,

Sidney,

Grifoni

et al. 2023

Cell Mol Immunol

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Antigen-specific T-cell recognition is restricted by Major Histocompatibility Complex (MHC) molecules, and differences between CD4 and CD8 immunogenicity in humans and animal species used in preclinical vaccine testing are yet to be fully understood. In this study, we addressed this matter by analyzing experimentally identified epitopes based on published data curated in the Immune Epitopes DataBase (IEDB) database. We first analyzed SARS-CoV-2 spike (S) and nucleoprotein (N), which are two common targets of the immune response and well studied in both human and mouse systems. We observed a weak but statistically significant correlation between human and H-2b mouse T-cell responses (CD8 S specific (r = 0.206, p = 1.37 × 10−13); CD4 S specific (r = 0.118, p = 2.63 × 10−5) and N specific (r = 0.179, p = 2.55 × 10−4)). Due to intrinsic differences in MHC molecules across species, we also investigated the association between the immunodominance of common Human Leukocyte Antigen (HLA) alleles for which HLA transgenic mice are available, namely, A*02:01, B*07:02, DRB1*01:01, and DRB1*04:01, and found higher significant correlations for both CD8 and CD4 (maximum r = 0.702, p = 1.36 × 10−31 and r = 0.594, p = 3.04−122, respectively). Our results further indicated that some regions are commonly immunogenic between humans and mice (either H-2b or HLA transgenic) but that others are human specific. Finally, we noted a significant correlation between CD8 and CD4 S- (r = 0.258, p = 7.33 × 1021) and N-specific (r = 0.369, p = 2.43 × 1014) responses, suggesting that discrete protein subregions can be simultaneously recognized by T cells. These findings were confirmed in other viral systems, providing general guidance for the use of murine models to test T-cell immunogenicity of viral antigens destined for human use.

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In-silico evaluation of the T-cell based immune response against SARS-CoV-2 omicron variants

Sharma,

Roy,

Cherian

2024

Sci Rep

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SARS-CoV-2 Omicron (BA.1 and BA.2) specific novel CD8+ and CD4+ T cell epitopes targeting spike protein

Cited by 4 publications

References 63 publications

Novel Methodology for the Design of Personalized Cancer Vaccine Targeting Neoantigens: Application to Pancreatic Ductal Adenocarcinoma.

Novel Methodology for the Design of Personalized Cancer Vaccine Targeting Neoantigens: Application to Pancreatic Ductal Adenocarcinoma.

Correlative CD4 and CD8 T-cell immunodominance in humans and mice: Implications for preclinical testing

In-silico evaluation of the T-cell based immune response against SARS-CoV-2 omicron variants

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