Tiantan vaccinia virus-based vaccine with promising safety provides sustained protection against mpox in non-human primates

Lin Zhu, Shuyuan Pan, Baoying Huang, Junjie Zhang, Zhaona Yang, Zhe Cong, Jianrong Ma, Shaoting Qiu, Yang Liu, Jingjing Zhang, Na Li, Jiahan Lu, Ting Chen, Yongzhi Hou, Dong Zhang, Qiang Wei, Dan Li (), Wenjie Tan (), Yuntao Zhang () and Jing Xue ()
Additional contact information
Lin Zhu: Chinese Academy of Medical Sciences and Peking Union Medical College
Shuyuan Pan: Beijing Institute of Biological Products Company Limited
Baoying Huang: Chinese Center for Disease Control and Prevention
Junjie Zhang: Chinese Center for Disease Control and Prevention
Zhaona Yang: Beijing Institute of Biological Products Company Limited
Zhe Cong: Chinese Academy of Medical Sciences and Peking Union Medical College
Jianrong Ma: Chinese Academy of Medical Sciences and Peking Union Medical College
Shaoting Qiu: Beijing Institute of Biological Products Company Limited
Yang Liu: Beijing Institute of Biological Products Company Limited
Jingjing Zhang: Chinese Academy of Medical Sciences and Peking Union Medical College
Na Li: Chinese Academy of Medical Sciences and Peking Union Medical College
Jiahan Lu: Chinese Academy of Medical Sciences and Peking Union Medical College
Ting Chen: Chinese Academy of Medical Sciences and Peking Union Medical College
Yongzhi Hou: Chinese Academy of Medical Sciences and Peking Union Medical College
Dong Zhang: Chinese Academy of Medical Sciences and Peking Union Medical College
Qiang Wei: Chinese Academy of Medical Sciences and Peking Union Medical College
Dan Li: Chinese Center for Disease Control and Prevention
Wenjie Tan: Chinese Center for Disease Control and Prevention
Yuntao Zhang: Beijing Institute of Biological Products Company Limited
Jing Xue: Chinese Academy of Medical Sciences and Peking Union Medical College

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract The World Health Organization (WHO) has declared the mpox outbreak a public health emergency of international concern (PHEIC). Safe and efficient vaccines against the mpox virus (MPXV) are urgently needed to impede the surge in cases. Here, we report the results of a preclinical study employing different dosing strategies on a vaccine candidate named NTV, obtained via targeted gene deletion in the Tiantan strain vaccinia virus, resulting in a replication-deficient variant. Following optimisation of the NTV immunization dose and confirmation of its protective efficacy against MPXV in a mouse model, we demonstrate that a two-shot NTV regimen in macaques elicits significant neutralizing antibody and cellular immune responses, providing efficient protection against MPXV challenge. Notably, we find that a single NTV dose or long-term immunization in macaques offer effective protection against moderate or severe mpox disease by enhancing cellular immunity and rapidly evoking neutralizing antibodies. These results demonstrate the vaccine’s potential for emergency use and for long-lasting protection. Safety evaluations show no adverse effects in macaques receiving triple the standard dosage in three consecutive injections. These findings highlight the potential of the NTV vaccine candidate with key advantages, including robust immunogenicity, sustained protective efficacy, and safety in preclinical settings.

Date: 2025
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DOI: 10.1038/s41467-025-62594-0

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