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The T-cell-directed vaccine BNT162b4 encoding conserved non-spike antigens protects animals from severe SARS-CoV-2 infection.
Arieta, Christina M; Xie, Yushu Joy; Rothenberg, Daniel A; Diao, Huitian; Harjanto, Dewi; Meda, Shirisha; Marquart, Krisann; Koenitzer, Byron; Sciuto, Tracey E; Lobo, Alexander; Zuiani, Adam; Krumm, Stefanie A; Cadima Couto, Carla Iris; Hein, Stephanie; Heinen, André P; Ziegenhals, Thomas; Liu-Lupo, Yunpeng; Vogel, Annette B; Srouji, John R; Fesser, Stephanie; Thanki, Kaushik; Walzer, Kerstin; Addona, Theresa A; Türeci, Özlem; Sahin, Ugur; Gaynor, Richard B; Poran, Asaf.
Afiliação
  • Arieta CM; BioNTech US, 40 Erie Street, Cambridge, MA 02139, USA. Electronic address: christina.arieta@biontech.us.
  • Xie YJ; BioNTech US, 40 Erie Street, Cambridge, MA 02139, USA.
  • Rothenberg DA; BioNTech US, 40 Erie Street, Cambridge, MA 02139, USA.
  • Diao H; BioNTech US, 40 Erie Street, Cambridge, MA 02139, USA.
  • Harjanto D; BioNTech US, 40 Erie Street, Cambridge, MA 02139, USA.
  • Meda S; BioNTech US, 40 Erie Street, Cambridge, MA 02139, USA.
  • Marquart K; BioNTech US, 40 Erie Street, Cambridge, MA 02139, USA.
  • Koenitzer B; BioNTech US, 40 Erie Street, Cambridge, MA 02139, USA.
  • Sciuto TE; BioNTech US, 40 Erie Street, Cambridge, MA 02139, USA.
  • Lobo A; BioNTech US, 40 Erie Street, Cambridge, MA 02139, USA.
  • Zuiani A; BioNTech US, 40 Erie Street, Cambridge, MA 02139, USA.
  • Krumm SA; BioNTech SE, An der Goldgrube 12, 55131 Mainz, Germany.
  • Cadima Couto CI; BioNTech SE, An der Goldgrube 12, 55131 Mainz, Germany.
  • Hein S; BioNTech SE, An der Goldgrube 12, 55131 Mainz, Germany.
  • Heinen AP; BioNTech SE, An der Goldgrube 12, 55131 Mainz, Germany.
  • Ziegenhals T; BioNTech SE, An der Goldgrube 12, 55131 Mainz, Germany.
  • Liu-Lupo Y; BioNTech US, 40 Erie Street, Cambridge, MA 02139, USA.
  • Vogel AB; BioNTech SE, An der Goldgrube 12, 55131 Mainz, Germany.
  • Srouji JR; BioNTech US, 40 Erie Street, Cambridge, MA 02139, USA.
  • Fesser S; BioNTech SE, An der Goldgrube 12, 55131 Mainz, Germany.
  • Thanki K; BioNTech SE, An der Goldgrube 12, 55131 Mainz, Germany.
  • Walzer K; BioNTech SE, An der Goldgrube 12, 55131 Mainz, Germany.
  • Addona TA; BioNTech US, 40 Erie Street, Cambridge, MA 02139, USA.
  • Türeci Ö; BioNTech SE, An der Goldgrube 12, 55131 Mainz, Germany; HI-TRON - Helmholtz Institute for Translational Oncology Mainz by DKFZ, Obere Zahlbacherstr. 63, 55131 Mainz, Germany.
  • Sahin U; BioNTech SE, An der Goldgrube 12, 55131 Mainz, Germany; TRON gGmbH - Translational Oncology at the University Medical Center of the Johannes Gutenberg University, Freiligrathstraße 12, 55131 Mainz, Germany.
  • Gaynor RB; BioNTech US, 40 Erie Street, Cambridge, MA 02139, USA.
  • Poran A; BioNTech US, 40 Erie Street, Cambridge, MA 02139, USA. Electronic address: asaf.poran@biontech.us.
Cell ; 186(11): 2392-2409.e21, 2023 05 25.
Article em En | MEDLINE | ID: mdl-37164012
ABSTRACT
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+ and CD8+ 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).
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: COVID-19 / Vacina BNT162 Limite: Animals / Humans Idioma: En Revista: Cell Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: COVID-19 / Vacina BNT162 Limite: Animals / Humans Idioma: En Revista: Cell Ano de publicação: 2023 Tipo de documento: Article