tetano
Editor, Senior Moderator
J Med Virol
. 2024 Feb;96(2):e29452.
doi: 10.1002/jmv.29452. Landscape of T cell epitopes displays hot mutations of SARS-CoV-2 variant spikes evading cellular immunity
Mengze Gan[SUP] 1 [/SUP], Jinge Cao[SUP] 1 [/SUP], Yandi Zhang[SUP] 1 [/SUP], Hui Fu[SUP] 1 [/SUP], Xiaosong Lin[SUP] 1 [/SUP], Qi Ouyang[SUP] 1 [/SUP], Xinyue Xu[SUP] 1 [/SUP], Yin Yuan[SUP] 2 [/SUP], Xionglin Fan[SUP] 1 [/SUP]
Affiliations
The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been accompanied by the emergence of viral mutations that pose a great challenge to existing vaccine strategies. It is not fully understood with regard to the role of mutations on the SARS-CoV-2 spike protein from emerging viral variants in T cell immunity. In the current study, recombinant eukaryotic plasmids were constructed as DNA vaccines to express the spike protein from multiple SARS-CoV-2 strains. These DNA vaccines were used to immunize BALB/c mice, and cross-T cell responses to the spike protein from these viral strains were quantitated using interferon-γ (IFN-γ) Elispot. Peptides covering the full-length spike protein from different viral strains were used to detect epitope-specific IFN-γ[SUP]+[/SUP] CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell responses by fluorescence-activated cell sorting. SARS-CoV-2 Delta and Omicron BA.1 strains were found to have broad T cell cross-reactivity, followed by the Beta strain. The landscapes of T cell epitopes on the spike protein demonstrated that at least 30 mutations emerging from Alpha to Omicron BA.5 can mediate the escape of T cell immunity. Omicron and its sublineages have 19 out of these 30 mutations, most of which are new, and a few are inherited from ancient circulating variants of concerns. The cross-T cell immunity between SARS-CoV-2 prototype strain and Omicron strains can be attributed to the T cell epitopes located in the N-terminal domain (181-246 aa [amino acids], 271-318 aa) and C-terminal domain (1171-1273 aa) of the spike protein. These findings provide in vivo evidence for optimizing vaccine manufacturing and immunization strategies for current or future viral variants.
Keywords: DNA vaccine; S protein; SARS-CoV-2; T cell epitope; cross-T cell response; immune evasion; the NTD region and the C terminus; the RBD and HR1 region.
. 2024 Feb;96(2):e29452.
doi: 10.1002/jmv.29452. Landscape of T cell epitopes displays hot mutations of SARS-CoV-2 variant spikes evading cellular immunity
Mengze Gan[SUP] 1 [/SUP], Jinge Cao[SUP] 1 [/SUP], Yandi Zhang[SUP] 1 [/SUP], Hui Fu[SUP] 1 [/SUP], Xiaosong Lin[SUP] 1 [/SUP], Qi Ouyang[SUP] 1 [/SUP], Xinyue Xu[SUP] 1 [/SUP], Yin Yuan[SUP] 2 [/SUP], Xionglin Fan[SUP] 1 [/SUP]
Affiliations
- PMID: 38314852
- DOI: 10.1002/jmv.29452
The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been accompanied by the emergence of viral mutations that pose a great challenge to existing vaccine strategies. It is not fully understood with regard to the role of mutations on the SARS-CoV-2 spike protein from emerging viral variants in T cell immunity. In the current study, recombinant eukaryotic plasmids were constructed as DNA vaccines to express the spike protein from multiple SARS-CoV-2 strains. These DNA vaccines were used to immunize BALB/c mice, and cross-T cell responses to the spike protein from these viral strains were quantitated using interferon-γ (IFN-γ) Elispot. Peptides covering the full-length spike protein from different viral strains were used to detect epitope-specific IFN-γ[SUP]+[/SUP] CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell responses by fluorescence-activated cell sorting. SARS-CoV-2 Delta and Omicron BA.1 strains were found to have broad T cell cross-reactivity, followed by the Beta strain. The landscapes of T cell epitopes on the spike protein demonstrated that at least 30 mutations emerging from Alpha to Omicron BA.5 can mediate the escape of T cell immunity. Omicron and its sublineages have 19 out of these 30 mutations, most of which are new, and a few are inherited from ancient circulating variants of concerns. The cross-T cell immunity between SARS-CoV-2 prototype strain and Omicron strains can be attributed to the T cell epitopes located in the N-terminal domain (181-246 aa [amino acids], 271-318 aa) and C-terminal domain (1171-1273 aa) of the spike protein. These findings provide in vivo evidence for optimizing vaccine manufacturing and immunization strategies for current or future viral variants.
Keywords: DNA vaccine; S protein; SARS-CoV-2; T cell epitope; cross-T cell response; immune evasion; the NTD region and the C terminus; the RBD and HR1 region.