tetano
Editor, Senior Moderator
Cell
. 2023 Apr 13;S0092-8674(23)00403-8.
doi: 10.1016/j.cell.2023.04.007. Online ahead of print. The T-cell-directed vaccine BNT162b4 encoding conserved non-spike antigens protects animals from severe SARS-CoV-2 infection
Christina M Arieta[SUP] 1 [/SUP], Yushu Joy Xie[SUP] 2 [/SUP], Daniel A Rothenberg[SUP] 2 [/SUP], Huitian Diao[SUP] 2 [/SUP], Dewi Harjanto[SUP] 2 [/SUP], Shirisha Meda[SUP] 2 [/SUP], Krisann Marquart[SUP] 2 [/SUP], Byron Koenitzer[SUP] 2 [/SUP], Tracey E Sciuto[SUP] 2 [/SUP], Alexander Lobo[SUP] 2 [/SUP], Adam Zuiani[SUP] 2 [/SUP], Stefanie A Krumm[SUP] 3 [/SUP], Carla Iris Cadima Couto[SUP] 3 [/SUP], Stephanie Hein[SUP] 3 [/SUP], André P Heinen[SUP] 3 [/SUP], Thomas Ziegenhals[SUP] 3 [/SUP], Yunpeng Liu-Lupo[SUP] 2 [/SUP], Annette B Vogel[SUP] 3 [/SUP], John R Srouji[SUP] 2 [/SUP], Stephanie Fesser[SUP] 3 [/SUP], Kaushik Thanki[SUP] 3 [/SUP], Kerstin Walzer[SUP] 3 [/SUP], Theresa A Addona[SUP] 2 [/SUP], Özlem Türeci[SUP] 4 [/SUP], Uğur Şahin[SUP] 5 [/SUP], Richard B Gaynor[SUP] 2 [/SUP], Asaf Poran[SUP] 6 [/SUP]
Affiliations
T cell responses play an important role in protection against beta-coronavirus infections, including SARS-CoV-2, where they associate with decreased COVID-19 disease severity and duration. To enhance T cell immunity across epitopes infrequently altered in SARS-CoV-2 variants, we designed BNT162b4, an mRNA vaccine component that is intended to be combined with BNT162b2, the spike-protein-encoding vaccine. BNT162b4 encodes variant-conserved, immunogenic segments of the SARS-CoV-2 nucleocapsid, membrane, and ORF1ab proteins, targeting diverse HLA alleles. BNT162b4 elicits polyfunctional CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell responses to diverse epitopes in animal models, alone or when co-administered with BNT162b2 while preserving spike-specific immunity. Importantly, we demonstrate that BNT162b4 protects hamsters from severe disease and reduces viral titers following challenge with viral variants. These data suggest that a combination of BNT162b2 and BNT162b4 could reduce COVID-19 disease severity and duration caused by circulating or future variants. BNT162b4 is currently being clinically evaluated in combination with the BA.4/BA.5 Omicron-updated bivalent BNT162b2 (NCT05541861).
Keywords: COVID-19; HLA ligandomics; SARS-CoV-2; T cell responses; immune protection; mRNA T cell vaccine; vaccine design; viral variants.
. 2023 Apr 13;S0092-8674(23)00403-8.
doi: 10.1016/j.cell.2023.04.007. Online ahead of print. The T-cell-directed vaccine BNT162b4 encoding conserved non-spike antigens protects animals from severe SARS-CoV-2 infection
Christina M Arieta[SUP] 1 [/SUP], Yushu Joy Xie[SUP] 2 [/SUP], Daniel A Rothenberg[SUP] 2 [/SUP], Huitian Diao[SUP] 2 [/SUP], Dewi Harjanto[SUP] 2 [/SUP], Shirisha Meda[SUP] 2 [/SUP], Krisann Marquart[SUP] 2 [/SUP], Byron Koenitzer[SUP] 2 [/SUP], Tracey E Sciuto[SUP] 2 [/SUP], Alexander Lobo[SUP] 2 [/SUP], Adam Zuiani[SUP] 2 [/SUP], Stefanie A Krumm[SUP] 3 [/SUP], Carla Iris Cadima Couto[SUP] 3 [/SUP], Stephanie Hein[SUP] 3 [/SUP], André P Heinen[SUP] 3 [/SUP], Thomas Ziegenhals[SUP] 3 [/SUP], Yunpeng Liu-Lupo[SUP] 2 [/SUP], Annette B Vogel[SUP] 3 [/SUP], John R Srouji[SUP] 2 [/SUP], Stephanie Fesser[SUP] 3 [/SUP], Kaushik Thanki[SUP] 3 [/SUP], Kerstin Walzer[SUP] 3 [/SUP], Theresa A Addona[SUP] 2 [/SUP], Özlem Türeci[SUP] 4 [/SUP], Uğur Şahin[SUP] 5 [/SUP], Richard B Gaynor[SUP] 2 [/SUP], Asaf Poran[SUP] 6 [/SUP]
Affiliations
- PMID: 37164012
- DOI: 10.1016/j.cell.2023.04.007
T cell responses play an important role in protection against beta-coronavirus infections, including SARS-CoV-2, where they associate with decreased COVID-19 disease severity and duration. To enhance T cell immunity across epitopes infrequently altered in SARS-CoV-2 variants, we designed BNT162b4, an mRNA vaccine component that is intended to be combined with BNT162b2, the spike-protein-encoding vaccine. BNT162b4 encodes variant-conserved, immunogenic segments of the SARS-CoV-2 nucleocapsid, membrane, and ORF1ab proteins, targeting diverse HLA alleles. BNT162b4 elicits polyfunctional CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell responses to diverse epitopes in animal models, alone or when co-administered with BNT162b2 while preserving spike-specific immunity. Importantly, we demonstrate that BNT162b4 protects hamsters from severe disease and reduces viral titers following challenge with viral variants. These data suggest that a combination of BNT162b2 and BNT162b4 could reduce COVID-19 disease severity and duration caused by circulating or future variants. BNT162b4 is currently being clinically evaluated in combination with the BA.4/BA.5 Omicron-updated bivalent BNT162b2 (NCT05541861).
Keywords: COVID-19; HLA ligandomics; SARS-CoV-2; T cell responses; immune protection; mRNA T cell vaccine; vaccine design; viral variants.