T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV

Abstract

Over 12 years have elapsed since severe acute respiratory syndrome (SARS) triggered the first global alert for coronavirus infections. Virus transmission in humans was quickly halted by public health measures and human infections of SARS coronavirus (SARS-CoV) have not been observed since. However, other coronaviruses still pose a continuous threat to human health, as exemplified by the recent emergence of Middle East respiratory syndrome (MERS) in humans. The work on SARS-CoV widens our knowledge on the epidemiology, pathophysiology and immunology of coronaviruses and may shed light on MERS coronavirus (MERS-CoV). It has been confirmed that T-cell immunity plays an important role in recovery from SARS-CoV infection. Herein, we summarize T-cell immunological studies of SARS-CoV and discuss the potential cross-reactivity of the SARS-CoV-specific immunity against MERS-CoV, which may provide useful recommendations for the development of broad-spectrum vaccines against coronavirus infections.

Keywords: Cross-reactivity; Epitope; MERS-CoV; SARS-CoV; T-cell; Vaccine.

Fig. 1

T-cell antigenic peptides in SARS-CoV structural proteins and the conservation of the corresponding sequences in MERS-CoV. The sequences of the four major structural proteins of SARS-CoV were aligned with that of MERS-CoV. Identical residues are denoted in red and variable residues in white. Peptides with T-cell antigenicity are shown along the protein sequence. Peptides with CD8⁺ T-cell-specific antigenicity and CD4⁺ T-cell antigenicity are shown in blue and green, respectively.

Fig. 2

Milestones of research on humoral and T-cell immunity against SARS-CoV and MERS-CoV. A. Studies that evaluate SARS-CoV-specific memory antibody and cellular responses in SARS patients or recovered donors are summarized along the 12-year time axis after the outbreak of the SARS epidemic. Arrowheads point to the time of sampling. B. Studies on human immunity to MERS-CoV and the cross-reactivity of MERS-CoV and SARS-CoV are listed.

Fig. 3

Structures of SARS-CoV-derived T-cell peptides presented by HLA I molecules. Conformations of T-cell epitope peptides from SARS-CoV presented by HLA-A*0201 (A-C, PDB codes: 3I6G, 3I6K and 3TO2), HLA-A*2402 (D, PDB code: 3I6L), HLA-A*1101 (E, PDB code: 1X7Q) and HLA-B*1501 (F, PDB code: 3C9N). The peptides are shown as sticks and spheres in different colors. The names and the positions of residues in the peptides are denoted in black letters and numbers. Peptide Md3 (B) and its overlapping peptide Md3-C9 (C) are shown in the similar cyan color, and their residue positions are shown in the corresponding numbers. The peptide N1 (D) forms a bulged conformation that is stabilized by intra-chain hydrogen bonds (dashed black lines) and two water molecules (cyan).