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Predicting the Immunogenicity of T cell epitopes: From HIV to SARS-CoV-2.

ABSTRACT: We describe a physics-based learning model for predicting the immunogenicity of Cytotoxic T Lymphocyte (CTL) epitopes derived from diverse pathogens, given a Human Leukocyte Antigen (HLA) genotype. The model was trained and tested on experimental data on the relative immunodominance of CTL epitopes in Human Immunodeficiency Virus infection. The method is more accurate than publicly available models. Our model predicts that only a fraction of SARS-CoV-2 epitopes that have been predicted to bind to HLA molecules is immunogenic. The immunogenic CTL epitopes across all SARS-CoV-2 proteins are predicted to provide broad population coverage, but the immunogenic epitopes in the SARS-CoV-2 spike protein alone are unlikely to do so. Our model predicts that several immunogenic SARS-CoV-2 CTL epitopes are identical to those contained in low-pathogenicity coronaviruses circulating in the population. Thus, we suggest that some level of CTL immunity against COVID-19 may be present in some individuals prior to SARS-CoV-2 infection.

SUBMITTER: Gao A

PROVIDER: S-EPMC7241102 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Predicting the Immunogenicity of T cell epitopes: From HIV to SARS-CoV-2.

Gao Ang A Chen Zhilin Z Segal Florencia Pereyra FP Carrington Mary M Streeck Hendrik H Chakraborty Arup K AK Julg Boris B

bioRxiv : the preprint server for biology 20200515

We describe a physics-based learning model for predicting the immunogenicity of Cytotoxic T Lymphocyte (CTL) epitopes derived from diverse pathogens, given a Human Leukocyte Antigen (HLA) genotype. The model was trained and tested on experimental data on the relative immunodominance of CTL epitopes in Human Immunodeficiency Virus infection. The method is more accurate than publicly available models. Our model predicts that only a fraction of SARS-CoV-2 epitopes that have been predicted to bind t ...[more]

PMID: 32511339

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Project description:The surge of SARS-CoV-2 has created a wave of pandemic around the globe due to its high transmission rate. To contain this virus, researchers are working around the clock for a solution in the form of vaccine. Due to the impact of this pandemic, the economy and healthcare have immensely suffered around the globe. Thus, an efficient vaccine design is the need of the hour. Moreover, to have a generalised vaccine for heterogeneous human population, the virus genomes from different countries should be considered. Thus, in this work, we have performed genome-wide analysis of 10,664 SARS-CoV-2 genomes of 73 countries around the globe in order to identify the potential conserved regions for the development of peptide based synthetic vaccine viz. epitopes with high immunogenic and antigenic scores. In this regard, multiple sequence alignment technique viz. Clustal Omega is used to align the 10,664 SARS-CoV-2 virus genomes. Thereafter, entropy is computed for each genomic coordinate of the aligned genomes. The entropy values are then used to find the conserved regions. These conserved regions are refined based on the criteria that their lengths should be greater than or equal to 60 nt and their corresponding protein sequences are without any stop codons. Furthermore, Nucleotide BLAST is used to verify the specificity of the conserved regions. As a result, we have obtained 17 conserved regions that belong to NSP3, NSP4, NSP6, NSP8, RdRp, Helicase, endoRNAse, 2'-O-RMT, Spike glycoprotein, ORF3a protein, Membrane glycoprotein and Nucleocapsid protein. Finally, these conserved regions are used to identify the T-cell and B-cell epitopes with their corresponding immunogenic and antigenic scores. Based on these scores, the most immunogenic and antigenic epitopes are then selected for each of these 17 conserved regions. Hence, we have obtained 30 MHC-I and 24 MHC-II restricted T-cell epitopes with 14 and 13 unique HLA alleles and 21 B-cell epitopes for the 17 conserved regions. Moreover, for validating the relevance of these epitopes, the binding conformation of the MHC-I and MHC-II restricted T-cell epitopes are shown with respect to HLA alleles. Also, the physico-chemical properties of the epitopes are reported along with Ramchandran plots and Z-Scores and the population coverage is shown as well. Overall, the analysis shows that the identified epitopes can be considered as potential candidates for vaccine design.

Project description:BackgroundsTo date, the effects of SARS-CoV-2 vaccines on people living with HIV (PLWH) were mainly focused on messenger RNA (mRNA) and adenovirus vector-based vaccines, and little is known about the effects of inactivated virus-based vaccine. This study was designed to determine the effects of inactivated SARS-CoV-2 vaccines on PLWH.MethodsTwenty-four HIV-positive individuals and 24 healthy donors (HD) were respectively recruited from Malipo Country People's Hospital and community in Kunming city. Enumeration of lymphocyte and CD4+CD45RO+ memory T cells were evaluated by flow cytometry. Competitive ELISA was used to measure the level of Anti-SARS-CoV-2 neutralization antibody. Spearman or Pearson correlation analysis was used to analyze the relationship between laboratory indicators and neutralization antibodies in PLWH. T-cell responses (Th1, Th2, Th17, Treg) and intracellular expression of cytokines (IL-2 and TNF-α) in CD4 or CD8 were induced by spike protein in SARS-CoV-2 (SARS-2-S) and further measured by intracellular staining.ResultsCD4, B cells, CD4+CD45RO+ memory T cells in peripheral blood of PLWH are dramatically decreased in comparison with HD. Importantly, PLWH display comparable neutralizing antibody positive rate to HD after inoculation with inactivated SARS-CoV-2 vaccine. However, PLWH showed weaker responses to vaccines exhibited by lower levels of neutralizing antibodies. Correlation analysis shows that this is possibly caused by low number of CD4 and B cells. Furthermore, SARS-2-S-induced Th2 and Th17 responses are also decreased in PLWH, while no influences on Treg and other cytokines (IL-2, TNF-α and IFN-γ) observed.ConclusionsPLWH and HD have comparable neutralizing antibodies positive rates, but PLWH display weaker responses to inactivated SARS-CoV-2 vaccines in magnitude, which suggests that a booster dose or dose adjustment are required for HIV-infected individuals, especially for those with lower counts of CD4 T and B cells.

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Predicting the Immunogenicity of T cell epitopes: From HIV to SARS-CoV-2.

Publications

Predicting the Immunogenicity of T cell epitopes: From HIV to SARS-CoV-2.

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