The T-cell-directed vaccine BNT162b4 encoding conserved non-spike antigens protects animals from severe SARS-CoV-2 infection

被引：49

作者：

Arieta, Christina M. ^{[1
]}

Xie, Yushu Joy ^{[1
]}

Rothenberg, Daniel A. ^{[1
]}

Diao, Huitian ^{[1
]}

Harjanto, Dewi ^{[1
]}

Meda, Shirisha ^{[1
]}

Marquart, Krisann ^{[1
]}

Koenitzer, Byron ^{[1
]}

Sciuto, Tracey E. ^{[1
]}

Lobo, Alexander ^{[1
]}

Zuiani, Adam ^{[1
]}

Krumm, Stefanie A. ^{[2
]}

Couto, Carla Iris Cadima ^{[2
]}

Hein, Stephanie ^{[2
]}

Heinen, Andre P. ^{[2
]}

Ziegenhals, Thomas ^{[2
]}

Liu-Lupo, Yunpeng ^{[1
]}

Vogel, Annette B. ^{[2
]}

Srouji, John R. ^{[1
]}

Fesser, Stephanie ^{[2
]}

Thanki, Kaushik ^{[2
]}

Walzer, Kerstin ^{[2
]}

Addona, Theresa A. ^{[1
]}

Tureci, Ozlem ^{[2
,3
]}

Sahin, Ugur ^{[2
,4
]}

Gaynor, Richard B. ^{[1
]}

Poran, Asaf ^{[1
]}

机构：

[1] BioNTech US, 40 Erie St, Cambridge, MA 02139 USA

[2] BioNTech SE, Goldgrube 12, D-55131 Mainz, Germany

[3] DKFZ, HI TRON Helmholtz Inst Translat Oncol Mainz, Obere Zahlbacherstr 63, D-55131 Mainz, Germany

[4] Johannes Gutenberg Univ Mainz, TRON gGmbH Translat Oncol, Univ Med Ctr, Freiligrathstr 12, D-55131 Mainz, Germany

来源：

CELL | 2023年 / 186卷 / 11期

关键词：

IMMUNITY; EPITOPE; RESPONSES; AIRWAY;

D O I：

10.1016/j.cell.2023.04.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 im-munity across epitopes infrequently altered in SARS-CoV-2 variants, we designed BNT162b4, an mRNA vac-cine 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, mem-brane, 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 sug-gest 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).

引用

页码：2392 / +

页数：40

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