tetano
Editor, Senior Moderator
Sci Adv
. 2025 Nov 21;11(47):eadx0037.
doi: 10.1126/sciadv.adx0037. Epub 2025 Nov 21. Conserved CD8 T cell vaccines without B cell epitopes drive robust protection against SARS-CoV-2 that is enhanced by intranasal boost
Genghao Chen[SUP] 1 2 [/SUP], Thao Nguyen[SUP] 3 4 [/SUP], Lindsay G A McKay[SUP] 5 [/SUP], Sravya Sowdamini Nakka[SUP] 5 [/SUP], Pan Hu[SUP] 5 [/SUP], Julia McBride[SUP] 1 2 [/SUP], Anthony C Liang[SUP] 1 2 [/SUP], Rachel Olson[SUP] 6 [/SUP], James J Moon[SUP] 3 4 7 8 [/SUP], Andrew D Luster[SUP] 3 4 7 [/SUP], Anthony Griffiths[SUP] 5 [/SUP], Stephen J Elledge[SUP] 1 2 [/SUP]
Affiliations
The emergence of SARS-CoV-2 variants has challenged the current spike protein-focused COVID-19 vaccine strategy due to neutralizing antibody escape and waning antibody-mediated immunity. In contrast, T cell-mediated immunity targeting conserved epitopes may offer broad and long-lasting protection. However, whether T cells alone can provide sufficient protection remains unclear. Here, we identified both Omicron BA.1-specific and ancestral (Wuhan)-conserved CD8 T cell epitopes in the SARS-CoV-2 spike protein and evaluated them as carrier-protein fusion vaccines in mouse models. Subcutaneous immunizations with two CD8 epitope peptides substantially lowered lung viral load and conferred protection against low-dose viral challenge, but not against high-dose challenge. Notably, intranasal boosting-with or without adjuvant-enhanced lung resident memory T cell responses and conferred potent, durable protection against high-dose infection. These findings emphasize the importance of mucosal vaccination to boost protective T cell immunity against SARS-CoV-2 and support the potential of T cell-based vaccines targeting conserved epitopes for broad immunity against SARS-CoV-2 and other respiratory viral threats.
. 2025 Nov 21;11(47):eadx0037.
doi: 10.1126/sciadv.adx0037. Epub 2025 Nov 21. Conserved CD8 T cell vaccines without B cell epitopes drive robust protection against SARS-CoV-2 that is enhanced by intranasal boost
Genghao Chen[SUP] 1 2 [/SUP], Thao Nguyen[SUP] 3 4 [/SUP], Lindsay G A McKay[SUP] 5 [/SUP], Sravya Sowdamini Nakka[SUP] 5 [/SUP], Pan Hu[SUP] 5 [/SUP], Julia McBride[SUP] 1 2 [/SUP], Anthony C Liang[SUP] 1 2 [/SUP], Rachel Olson[SUP] 6 [/SUP], James J Moon[SUP] 3 4 7 8 [/SUP], Andrew D Luster[SUP] 3 4 7 [/SUP], Anthony Griffiths[SUP] 5 [/SUP], Stephen J Elledge[SUP] 1 2 [/SUP]
Affiliations
- PMID: 41270167
- PMCID: PMC12637294
- DOI: 10.1126/sciadv.adx0037
The emergence of SARS-CoV-2 variants has challenged the current spike protein-focused COVID-19 vaccine strategy due to neutralizing antibody escape and waning antibody-mediated immunity. In contrast, T cell-mediated immunity targeting conserved epitopes may offer broad and long-lasting protection. However, whether T cells alone can provide sufficient protection remains unclear. Here, we identified both Omicron BA.1-specific and ancestral (Wuhan)-conserved CD8 T cell epitopes in the SARS-CoV-2 spike protein and evaluated them as carrier-protein fusion vaccines in mouse models. Subcutaneous immunizations with two CD8 epitope peptides substantially lowered lung viral load and conferred protection against low-dose viral challenge, but not against high-dose challenge. Notably, intranasal boosting-with or without adjuvant-enhanced lung resident memory T cell responses and conferred potent, durable protection against high-dose infection. These findings emphasize the importance of mucosal vaccination to boost protective T cell immunity against SARS-CoV-2 and support the potential of T cell-based vaccines targeting conserved epitopes for broad immunity against SARS-CoV-2 and other respiratory viral threats.