A multifaceted approach for identification, validation, and immunogenicity of naturally processed and in silico-predicted highly conserved SARS-CoV-2 peptides

• Published in: Vaccine Vol. 42; no. 2; pp. 162 - 174
• Main Authors: Ratishvili, Tamar, Quach, Huy Quang, Haralambieva, Iana H., Suryawanshi, Yogesh R., Ovsyannikova, Inna G., Kennedy, Richard B., Poland, Gregory A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 12.01.2024; Elsevier Limited
• Subjects: Algorithms; Allergy and Immunology; Antibodies; Antigens; Apheresis; Cancer; Cell culture; Cell lines; Cellular immunity; Chromatography, Liquid; class; COVID-19; COVID-19 - prevention & control; COVID-19 Vaccines; Epitope prediction; Epitopes; Epitopes, T-Lymphocyte; HLA molecules; Humans; Immunogenicity; Immunopeptidomics; Infections; Liquid chromatography; longevity; Lymphocytes; Lymphocytes T; Mass spectrometry; Mass spectroscopy; Medical research; Peptide libraries; Peptide vaccines; Peptides; prediction; Proteins; Public health; SARS-CoV-2; SARS-CoV-2 vaccines; Scientific imaging; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus; T-lymphocytes; Tandem Mass Spectrometry; Vaccines; Viral Vaccines; World population; United States > US; Immunopeptidomics; SARS-CoV-2; Epitope prediction; SARS-CoV-2 vaccines; HLA molecules; Cellular immunity; Mass spectrometry; Peptide vaccines
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2023.12.024

SARS-CoV-2 remains a major global public health concern. Antibody waning and immune escape variant emergence necessitate the development of next generation vaccines that induce cross-reactive durable immune responses. T cell responses to SARS-CoV-2 demonstrate higher conservation, antigenic breadth, and longevity than antibody responses. Therefore, we sought to identify pathogen-derived T cell epitopes for a potential peptide-based vaccine. We pursued an approach leveraging: 1) liquid chromatography and tandem mass spectrometry (LC-MS/MS)-based identification of peptides from ancestral SARS-CoV-2-infected cell lines, 2) epitope prediction algorithms, and 3) overlapping peptide libraries. From this strategy, we identified 380 unique SARS-CoV-2-derived peptide sequences, including 53 antigenic HLA class I and class II peptides from multiple structural and non-structural/accessory viral proteins. These peptide sequences were highly conserved across variants of concern/interest (VoC/VoIs), and are estimated to achieve coverage of >96% of the world population. Our findings validate this discovery pipeline for peptide identification and immunogenicity testing, and are a crucial step toward the development of a next-generation multi-epitope SARS-CoV-2 peptide vaccine, and a novel vaccine platform methodology.