Tiantan vaccinia virus-based vaccine with promising safety provides sustained protection against mpox in non-human primates
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.
Authors
- Qiang Wei (ORCID: https://orcid.org/0000-0001-8914-1069)
- Lin Zhu (ORCID: https://orcid.org/0000-0001-5772-9482)
- Jing Xue (ORCID: https://orcid.org/0000-0002-9113-2433)
- Jiahan Lu
- Zhaona Yang
- Wenjie Tan
- Baoying Huang (ORCID: https://orcid.org/0000-0003-3766-6968)
- Shu-Yuan Pan (ORCID: https://orcid.org/0000-0003-2082-4077)
- Ting Chen
- Junjie Zhang (ORCID: https://orcid.org/0000-0002-0855-4118)
- Yang Liu (ORCID: https://orcid.org/0000-0002-0367-8189)
- Dong Zhang (ORCID: https://orcid.org/0000-0001-5454-1396)
- Na Li (ORCID: https://orcid.org/0000-0002-0404-6431)
- Jingjing Zhang (ORCID: https://orcid.org/0000-0002-7281-7429)
- Dan Li (ORCID: https://orcid.org/0000-0003-1596-8033)
- Shaoting Qiu
- Jianrong Ma
- Zhe Cong
- Yongzhi Hou
- Yuntao Zhang (ORCID: https://orcid.org/0009-0006-9134-5582)
Institutions
- Chinese Center For Disease Control and Prevention (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- China National Pharmaceutical Group Corporation (China) (CN)
- National Vaccine and Serum Institute (CN)
- Sino Biological (China) (CN)
- National Center for AIDS/STD Control and Prevention,China CDC (CN)
- Institute of Laboratory Animal Science (CN)
- National Institute for Viral Disease Control and Prevention (CN)
- National Institute for Communicable Disease Control and Prevention (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-05
- DOI
- https://doi.org/10.1038/s41467-025-62594-0
- Citations
- 3
- Primary Topic
- Poxvirus research and outbreaks
- Type
- article
- Field-Weighted Citation Impact
- 3.11
Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Chinese Academy of Medical Sciences
- Institute of Microbiology, Chinese Academy of Sciences