一种多价信使核糖核酸猴痘病毒疫苗（BNT166）可保护小鼠和猕猴免受正痘病毒疾病侵害。

A multivalent mRNA monkeypox virus vaccine (BNT166) protects mice and macaques from orthopoxvirus disease.

作者信息

Zuiani Adam, Dulberger Charles L, De Silva Nilushi S, Marquette Meghan, Lu Yu-Jung, Palowitch Gavin M, Dokic Anja, Sanchez-Velazquez Ricardo, Schlatterer Katja, Sarkar Sanjay, Kar Swagata, Chawla Bhavna, Galeev Alibek, Lindemann Claudia, Rothenberg Daniel A, Diao Huitian, Walls Alexandra C, Addona Theresa A, Mensa Federico, Vogel Annette B, Stuart Lynda M, van der Most Robbert, Srouji John R, Türeci Özlem, Gaynor Richard B, Şahin Uğur, Poran Asaf

机构信息

BioNTech US, Cambridge, MA 02139, USA.

BioNTech SE, Mainz, Germany.

出版信息

Cell. 2024 Mar 14;187(6):1363-1373.e12. doi: 10.1016/j.cell.2024.01.017. Epub 2024 Feb 15.

DOI:10.1016/j.cell.2024.01.017

PMID:38366591

Abstract

In response to the 2022 outbreak of mpox driven by unprecedented human-to-human monkeypox virus (MPXV) transmission, we designed BNT166, aiming to create a highly immunogenic, safe, accessible, and scalable next-generation vaccine against MPXV and related orthopoxviruses. To address the multiple viral forms and increase the breadth of immune response, two candidate multivalent mRNA vaccines were evaluated pre-clinically: a quadrivalent vaccine (BNT166a; encoding the MPXV antigens A35, B6, M1, H3) and a trivalent vaccine (BNT166c; without H3). Both candidates induced robust T cell responses and IgG antibodies in mice, including neutralizing antibodies to both MPXV and vaccinia virus. In challenge studies, BNT166a and BNT166c provided complete protection from vaccinia, clade I, and clade IIb MPXV. Furthermore, immunization with BNT166a was 100% effective at preventing death and at suppressing lesions in a lethal clade I MPXV challenge in cynomolgus macaques. These findings support the clinical evaluation of BNT166, now underway (NCT05988203).

摘要

为应对由前所未有的人际传播猴痘病毒（MPXV）引发的2022年猴痘疫情，我们设计了BNT166，旨在打造一种针对MPXV及相关正痘病毒的具有高免疫原性、安全性、可及性且可扩展的下一代疫苗。为应对多种病毒形式并增强免疫反应的广度，我们在临床前评估了两种候选多价mRNA疫苗：一种四价疫苗（BNT166a；编码MPXV抗原A35、B6、M1、H3）和一种三价疫苗（BNT166c；不含H3）。两种候选疫苗均在小鼠体内诱导了强烈的T细胞反应和IgG抗体，包括针对MPXV和痘苗病毒的中和抗体。在攻毒研究中，BNT166a和BNT166c对痘苗病毒、I分支和IIb分支MPXV提供了完全保护。此外，在食蟹猴的致死性I分支MPXV攻毒实验中，用BNT166a免疫在预防死亡和抑制损伤方面的有效性达100%。这些发现支持了目前正在进行的BNT166的临床评估（NCT05988203）。