Identification of a dominant CD8+ CTL epitope in the SARS-associated coronavirus 2 spike protein

Abstract

Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, has been spreading throughout the world. To date, there are still no approved human vaccines for this disease. To develop an effective vaccine, the establishment of animal models for evaluating post-vaccination immune responses is necessary. In this study, we have identified a CTL epitope in the SARS-CoV-2 spike (S) protein that could be used to measure the cellular immune response against this protein. Potential predicted CTL epitopes of the SARS-CoV-2 S protein were investigated by immunizing BALB/c mice with a recombinant of the receptor-binding domain (RBD) of the S protein. Then, CD8 + T cells specific for S-RBD were detected by stimulating with potential epitope peptides and then measuring the interferon-gamma production. Truncation of this peptide revealed that S-RBD-specific CD8 + T cells recognized a D d -restricted S 526–533 peptide. In conclusion, this animal model is suitable for evaluating the immunogenicity of SARS-CoV-2 vaccines.

Intranasal Administration of RBD Nanoparticles Confers Induction of Mucosal and Systemic Immunity against SARS-CoV-2

“…In particular, for CD8 + cells, the magnitude of CTL responses was stronger in RBD-TMC NP immunized mice, when compared with sRBD administration. This is in accordance with previous studies showing that RBD protein was immunogenic to splenic T cells in murine models in which the immunodominant epitopes of RBD corresponded to S 375-394 , S 405-469 , S 495-521 and S 526-533 [ 11 , 48 ]. The RBD used in our present study contained these T cell epitopes.…”

“…These regions play a key role in recognizing host receptors and mediating the fusion of the viral envelope and host membrane, respectively. Epitope mapping of the S-glycoprotein revealed the RBD as a major target for neutralizing antibodies, and identified many peptides on this protein as dominant T cell epitopes [ 9 , 10 , 11 , 12 ], suggesting that RBD may be a promising candidate for a SARS-CoV-2 vaccine.…”

Identification of a Promiscuous Conserved CTL Epitope Within the SARS-CoV-2 Spike Protein

“…Additionally, lymphopenia was more accentuated in symptomatic COVID-19 patients with pneumonia than in those without pneumonia, consistent with T cell immunity playing a protective role in pre-existing immunity against SARS-CoV-2 [17][18][19] . However, the role of T cell immunity in the pathology of COVID-19 has not been clari ed 20 and awaits further de nition of T cell epitopes and their functions. Engineered improvements in the peptide epitopes recognized by CTL have been an essential feature of the advancements made in evaluating the cellular immunity induced by vaccines.…”

“…There is a lack of information on the CD8+ T cellrecognized epitopes within the spike antigen; consequently, only overlapping peptide pools that covered the whole region of spike antigen have been used routinely to evaluate cell-mediated immunity (CMI) of a vaccine candidate 6,7,8 . However, a few reports had suggested that CTL epitopes are present within the spike protein 9 , but no detailed mapping information had been reported or potential sequences discovered. The identi cation of those CD8+ T cell epitopes would provide an important tool to evaluate the T cell immunity in vaccinated individuals or patients and was undertaken here.…”

Identification of a promiscuous conserved CTL epitope within the SARS-CoV-2 spike protein

“…There is a lack of information on the CD8+ T cell-recognized epitopes within the spike antigen; consequently, only overlapping peptide pools that covered the whole region of spike antigen have been used routinely to evaluate cell-mediated immunity (CMI) of a vaccine candidate 6,7,8 . However, a few reports had suggested that CTL epitopes are present within the spike protein 9 , but no detailed mapping information had been reported or potential sequences discovered. The identification of those CD8+ T cell epitopes would provide an important tool to evaluate the T cell immunity in vaccinated individuals or patients and was undertaken here.…”