Landscape and Selection of Vaccine Epitopes in SARS-CoV-2
Description
The COVID-19 pandemic is a worldwide public health crisis. A vaccine with efficacy against SARS-CoV-2, the pathogen that causes COVID-19, is needed. While most vaccines under investigation are optimized to generate an antibody response, we hypothesize that peptide vaccines containing optimized epitope regions with concurrent B cell, CD4+ T cell, and CD8+ T cell stimulation would drive both humoral and cellular immunity with high specificity, potentially avoiding undesired effects such as antibody-dependent enhancement (ADE), all the while providing a platform with fast manufacturing potential and with high shelf-life stability. Here we combine computational prediction of T cell epitopes with recently published B cell epitope mapping studies to propose optimized peptide vaccines for SARS-CoV-2. We begin with an exploration of the predicted T cell epitope space in SARS-CoV-2, with interrogation of HLA-I and -II epitope overlap, protein source, concurrent human/murine coverage, and allelic space. The T cell vaccine candidates were selected by further considering their predicted affinities for MHC-I and MHC-II alleles across the human population (as well as H2-b/H2-d murine coverage to support preclinical studies), predicted immunogenicity, viral protein abundance, sequence conservation, and co-localization of MHC-I and -II epitopes. The predicted B cell epitope regions were selected by starting from responses identified in linear epitope mapping studies of patient serum and filtering to select those with high molecular dynamics-derived surface accessibility, high sequence conservation, spatial localization within functional domains of the spike glycoprotein (RBD, FP, and HR regions), and avoidance of glycosylation sites. From 58 initial candidates, three B cell epitope regions were identified using these criteria. By combining these B cell and T cell analyses, we propose a set of human and murine-compatible SARS-CoV-2 vaccine peptide candidates.