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

作者：Adam Zuiani, Charles L. Dulberger, Nilushi S. De Silva, Meghan Marquette, Yu-Jung Lu, Gavin M. Palowitch, Anja Dokic, Ricardo Sanchez-Velazquez, Katja Schlatterer, Sanjay Sarkar, Swagata Kar, Bhavna Chawla, Alibek Galeev, Claudia Lindemann, Daniel Rothenberg, Huitian Diao, Alexandra C. Walls, Theresa A. Addona, Federico Mensa, Annette B. Vogel, Lynda M. Stuart, Robbert van der Most, John Srouji, Özlem Türeci, Richard B. Gaynor, Uğur Şahin, Asaf Poran · 发表于：Cell · 年份：2024 · DOI：10.1016/j.cell.2024.01.017 · 被引用次数：159 · 研究领域：Poxvirus research and outbreaks、Herpesvirus Infections and Treatments、Bacillus and Francisella bacterial research

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).