RESUMO
There is significant interest in T-cell mediated immunity against SARS-CoV-2. Both vaccination and infection have been observed to elicit durable T-cell responses against the virus. The classical role of CD4+ T-cell responses in coordinating humoral immunity is well understood but it is less clear to what degree, if any, T-cell responses play a direct protective role against infection In this study we vaccinated BALB/c mice with peptides derived from the SARS-CoV-2 proteome designed to either elicit T-cell responses or B-cell responses against linear epitopes. These peptides were administered in combination with either of two adjuvants, poly(I:C) and the STING agonist BI-1387466. Both adjuvants consistently elicited responses against the same peptides, preferentially from the group selected for predicted T-cell immunogenicity. The magnitude of T-cell responses was, however, significantly higher with BI-1387466 compared with poly(I:C). Neither adjuvant group, however, provided any protection against infection with the murine adapted virus SARS-CoV-2-MA10 or from disease following infection.
RESUMO
There is an urgent need for a vaccine with efficacy against SARS-CoV-2. We hypothesize that peptide vaccines containing epitope regions optimized for 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). Additionally, such vaccines can be rapidly manufactured in a distributed manner. In this study, we combine computational prediction of T cell epitopes, recently published B cell epitope mapping studies, and epitope accessibility to select candidate peptide vaccines for SARS-CoV-2. We begin with an exploration of the space of possible T cell epitopes in SARS-CoV-2 with interrogation of predicted HLA-I and HLA-II ligands, overlap between predicted ligands, protein source, as well as concurrent human/murine coverage. Beyond MHC affinity, T cell vaccine candidates were further refined by predicted immunogenicity, viral source protein abundance, sequence conservation, coverage of high frequency HLA alleles and co-localization of CD4+ and CD8+ T cell epitopes. B cell epitope regions were chosen from linear epitope mapping studies of convalescent patient serum, followed by filtering to select regions with surface accessibility, high sequence conservation, spatial localization near functional domains of the spike glycoprotein, and avoidance of glycosylation sites. From 58 initial candidates, three B cell epitope regions were identified. By combining these B cell and T cell analyses, as well as a manufacturability heuristic, we propose a set of SARS-CoV-2 vaccine peptides for use in subsequent murine studies and clinical trials. O_FIG O_LINKSMALLFIG WIDTH=180 HEIGHT=200 SRC="FIGDIR/small/135004v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1fc6599org.highwire.dtl.DTLVardef@1725a45org.highwire.dtl.DTLVardef@84a233org.highwire.dtl.DTLVardef@1b4c7aa_HPS_FORMAT_FIGEXP M_FIG C_FIG
