Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

npj Vaccines
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. npj vaccines
  3. articles
  4. article
Recombinant vaccinia vectored ASFV vaccine enhances swine survival against genotype II challenge
Download PDF
Download PDF
  • Article
  • Open access
  • Published: 23 January 2026

Recombinant vaccinia vectored ASFV vaccine enhances swine survival against genotype II challenge

  • Lanlan Dong1,2 na1,
  • Nan Gao3 na1,
  • Renqiang Liu4 na1,
  • Kangli Cao1,
  • Ai Xia1,2,
  • Tianhan Yang2,
  • Xinghao Pan5,
  • Cuisong Zhu2,
  • Ziling Zhang1,
  • Dongming Zhao4,
  • Chen Zhao2,
  • Xiaoyan Zhang1,2 &
  • …
  • Jianqing Xu1,2,6 

npj Vaccines , Article number:  (2026) Cite this article

  • 569 Accesses

  • 1 Altmetric

  • Metrics details

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Vaccines
  • Viral vectors

Abstract

The African Swine Fever Virus (ASFV) poses a major threat to global livestock production by infecting both domestic and wild pigs, causing significant economic loss. Despite promising protective results observed with live attenuated viruses, the safety concern blocked its extensive application. In this study, we developed a novel vaccine combining two recombinant vaccinia viruses-rTTV-D-A and rTTV-K-J-that together express eight ASFV genes, including EP402R (CD2v), B646L (p72), B602L (pB602L), D117L (p17), H240R (pH240R), B438L (p49), E183L (p54), CP204L (p30), and a synthetic T antigen composed of conserved T cell epitopes from multiple ASFV proteins, aiming to induce both humoral and T-cell immune responses against different viral antigens. After demonstrating that this vaccine induced antigen-specific humoral and cellular responses in both mice and swine, its protective efficacy in swine was examined using a lethal challenge model. The vaccinated pigs showed a promising protection against the lethal challenge of a virulent genotype II ASFV strain (100 HAD50/pig), with 4 out of 6 surviving, while all control animals succumbed from 9 to 15 days post challenge. Importantly, the protection was further evidenced by the recovery to normal temperature and no ASFV infection-related clinical signs or virus shedding in surviving pigs over a 21-day observation period. Our results support the potential of rTTV-D-A and rTTV-K-J as a novel multi-immunogen vaccinia-vectored ASFV vaccine. Further studies are warranted to explore and improve its use as a standalone vaccine or in combination with other vaccine platforms to achieve broad and effective protection against ASFV.

Similar content being viewed by others

African swine fever vaccine ASFV-G-ΔI177L induces solid protection in four-week-old piglets

Article Open access 23 December 2025

Highly lethal genotype I and II recombinant African swine fever viruses detected in pigs

Article Open access 29 May 2023

Immunoinformatics-guided approach for designing a pan-proteome multi-epitope subunit vaccine against African swine fever virus

Article Open access 16 January 2024

Data availability

The DNA sequence of the MTCE used in the rTTV-D-A has been deposited in the DNA DataBank of Japan under accession number LC897646.

References

  1. Blome, S., Franzke, K. & Beer, M. African swine fever–A review of current knowledge. Virus Res. 287, 198099 (2020).

    Google Scholar 

  2. Kleiboeker, S. B. & Scoles, G. A. Pathogenesis of African swine fever virus in Ornithodoros ticks. Anim. Health Res. Rev. 2, 121–128 (2001).

    Google Scholar 

  3. Pereira De Oliveira, R. et al. Differential vector competence of Ornithodoros soft ticks for African swine fever virus: what if it involves more than just crossing organic barriers in ticks? Parasites Vectors 13, 1–15 (2020).

    Google Scholar 

  4. Li, Z. et al. African swine fever virus: a review. Life 12, 1255 (2022).

    Google Scholar 

  5. Ruedas-Torres, I., Thi to Nga, B. & Salguero, F. J. Pathogenicity and virulence of African swine fever virus. Virulence 15, 2375550 (2024).

    Google Scholar 

  6. Sánchez-Vizcaíno, J., Mur, L., Gomez-Villamandos, J. & Carrasco, L. An update on the epidemiology and pathology of African swine fever. J. Comp. Pathol. 152, 9–21 (2015).

    Google Scholar 

  7. Zhang, H. et al. Vaccines for African swine fever: an update. Front. Microbiol. 14, 1139494 (2023).

    Google Scholar 

  8. Dixon, L. K., Chapman, D. A., Netherton, C. L. & Upton, C. African swine fever virus replication and genomics. Virus Res. 173, 3–14 (2013).

    Google Scholar 

  9. Bastos, A. D. et al. Genotyping field strains of African swine fever virus by partial p72 gene characterisation. Arch. Virol. 148, 693–706 (2003).

    Google Scholar 

  10. Goatley, L. C. et al. African swine fever virus NAM P1/95 is a mixture of genotype I and genotype VIII viruses. Microbiol. Resour. Announc. 13, e00067–00024 (2024).

    Google Scholar 

  11. Njau, E. P. et al. African swine fever virus (ASFV): biology, genomics and genotypes circulating in sub-Saharan Africa. Viruses 13, 2285 (2021).

    Google Scholar 

  12. Ata, E. B. et al. African swine fever virus: a raised global upsurge and a continuous threaten to pig husbandry. Microb. Pathog. 167, 105561 (2022).

    Google Scholar 

  13. Zhao, D. et al. Highly lethal genotype I and II recombinant African swine fever viruses detected in pigs. Nat. Commun. 14, 3096 (2023).

    Google Scholar 

  14. Lee, K. et al. Molecular characterization of emerging recombinant African swine fever virus of genotype I and II in Vietnam, 2023. Emerg. Microbes Infect. 13, 2404156 (2024).

    Google Scholar 

  15. Igolkin, A. et al. Detection of the first recombinant African swine fever virus (genotypes I and II) in domestic pigs in Russia. Mol. Biol. Rep. 51, 1–9 (2024).

    Google Scholar 

  16. Vu, H. L. & McVey, D. S. Recent progress on gene-deleted live-attenuated African swine fever virus vaccines. npj Vaccines 9, 60 (2024).

    Google Scholar 

  17. van den Born, E. et al. African swine fever virus vaccine strain Asfv-G-∆ I177l reverts to virulence and negatively affects reproductive performance. npj Vaccines 10, 46 (2025).

    Google Scholar 

  18. Nguyen, T. C. et al. An African swine fever vaccine-like variant with multiple gene deletions caused reproductive failure in a Vietnamese breeding herd. Sci. Rep. 15, 14919 (2025).

    Google Scholar 

  19. Zhang, Y. et al. ASFV Subunit vaccines: strategies and prospects for future development. Microb. Pathog. 197, 107063 (2024).

    Google Scholar 

  20. Deng, Y. et al. Recombinant vaccinia vector-based vaccine (Tiantan) boosting a novel HBV subunit vaccine induced more robust and lasting immunity in rhesus macaques. Vaccine 35, 3347–3353 (2017).

    Google Scholar 

  21. Zhang, X. et al. TianTan vaccinia virus-based EBV vaccines targeting both latent and lytic antigens elicits potent immunity against lethal EBV challenge in humanized mice. Emerg. Microbes Infect. 13, 2412640 (2024).

    Google Scholar 

  22. Onisk, D. et al. Passively transferred African swine fever virus antibodies protect swine against lethal infection. Virology 198, 350–354 (1994).

    Google Scholar 

  23. Oura, C. A., Denyer, M., Takamatsu, H. & Parkhouse, R. In vivo depletion of CD8+ T lymphocytes abrogates protective immunity to African swine fever virus. J. Gen. Virol. 86, 2445–2450 (2005).

    Google Scholar 

  24. Alejo, A., Matamoros, T., Guerra, M. & Andrés, G. A proteomic atlas of the African swine fever virus particle. J. Virol. 92, 01293–01218 (2018).

    Google Scholar 

  25. Reis, A. L. et al. From structure prediction to function: defining the domain on the African swine fever virus CD2v protein required for binding to erythrocytes. mBio 16, e01655–01624 (2024).

    Google Scholar 

  26. Ruiz-Gonzalvo, F., Rodríguez, F. & Escribano, J. Functional and immunological properties of the baculovirus-expressed hemagglutinin of African swine fever virus. Virology 218, 285–289 (1996).

    Google Scholar 

  27. Liu, S. et al. Cryo-EM structure of the African swine fever virus. Cell Host microbe 26, 836–843.e833 (2019).

    Google Scholar 

  28. Cobbold, C., Windsor, M. & Wileman, T. A virally encoded chaperone specialized for folding of the major capsid protein of African swine fever virus. J. Virol. 75, 7221–7229 (2001).

    Google Scholar 

  29. Wang, N. et al. Architecture of African swine fever virus and implications for viral assembly. Science 366, 640–644 (2019).

    Google Scholar 

  30. Gomez-Puertas, P. et al. Neutralizing antibodies to different proteins of African swine fever virus inhibit both virus attachment and internalization. J. Virol. 70, 5689–5694 (1996).

    Google Scholar 

  31. Gómez-Puertas, P. et al. The African swine fever virus proteins p54 and p30 are involved in two distinct steps of virus attachment and both contribute to the antibody-mediated protective immune response. Virology 243, 461–471 (1998).

    Google Scholar 

  32. Barderas, M. et al. Antigenic and immunogenic properties of a chimera of two immunodominant African swine fever virus proteins. Arch. Virol. 146, 1681–1691 (2001).

    Google Scholar 

  33. Ding, M. et al. Sequential deletions of interferon inhibitors MGF110-9L and MGF505-7R result in sterile immunity against the Eurasia strain of Africa swine fever. J. Virol. 96, e01192–01122 (2022).

    Google Scholar 

  34. Tai, W. et al. An mRNA vaccine against monkeypox virus inhibits infection by co-activation of humoral and cellular immune responses. Nat. Commun. 16, 2971 (2025).

    Google Scholar 

  35. Li, Y. et al. A multivalent mRNA vaccine elicits robust immune responses and confers protection in a murine model of monkeypox virus infection. Nat. Commun. 16, 7373 (2025).

    Google Scholar 

  36. Argilaguet, J. M. et al. BacMam immunization partially protects pigs against sublethal challenge with African swine fever virus. Antivir. Res. 98, 61–65 (2013).

    Google Scholar 

  37. Argilaguet, J. M. et al. DNA vaccination partially protects against African swine fever virus lethal challenge in the absence of antibodies. PLoS ONE 7, e40942 (2012).

    Google Scholar 

  38. Lacasta, A. et al. Live attenuated African swine fever viruses as ideal tools to dissect the mechanisms involved in viral pathogenesis and immune protection. Vet. Res. 46, 1–16 (2015).

    Google Scholar 

  39. Petrovan, V. et al. Role of African swine fever virus proteins EP153R and EP402R in reducing viral persistence in blood and virulence in pigs infected with BeninΔDP148R. J. Virol. 96, e01340–01321 (2022).

    Google Scholar 

  40. Goatley, L. C. et al. A pool of eight virally vectored African swine fever antigens protect pigs against fatal disease. Vaccines 8, 234 (2020).

    Google Scholar 

  41. Portugal, R. et al. Six adenoviral vectored African swine fever virus genes protect against fatal disease caused by genotype I challenge. J. Virol. 98, e00622–e00624 (2024).

    Google Scholar 

  42. Liu, W. et al. A new vaccination regimen using adenovirus-vectored vaccine confers effective protection against African swine fever virus in swine. Emerg. Microbes Infect. 12, 2233643. https://doi.org/10.1080/22221751.2023.2233643 (2023).

    Google Scholar 

  43. Sun, E. et al. Emergence and prevalence of naturally occurring lower virulent African swine fever viruses in domestic pigs in China in 2020. Sci. China Life Sci. 64, 752–765 (2021).

    Google Scholar 

  44. Ge, S. et al. Molecular characterization of African swine fever virus, China, 2018. Emerg. Infect. Dis. 24, 2131 (2018).

    Google Scholar 

  45. Zajac, M. D. et al. Immunization of pigs with replication-incompetent adenovirus-vectored African swine fever virus multi-antigens induced humoral immune responses but no protection following contact challenge. Front. Vet. Sci. 10, 1208275 (2023).

    Google Scholar 

  46. Qin, L., Liang, M. & Evans, D. H. Genomic analysis of vaccinia virus strain TianTan provides new insights into the evolution and evolutionary relationships between Orthopoxviruses. Virology 442, 59–66 (2013).

    Google Scholar 

  47. Li, M. et al. Long-lasting humoral and cellular memory immunity to vaccinia virus Tiantan provides pre-existing immunity against mpox virus in Chinese population. Cell Rep. 43, 113609 (2024).

    Google Scholar 

  48. Drew, D. R., Lightowlers, M. & Strugnell, R. A. Humoral immune responses to DNA vaccines expressing secreted, membrane bound and non-secreted forms of the: Taenia ovis 45W antigen. Vaccine 18, 2522–2532 (2000).

    Google Scholar 

  49. Heo, J. et al. Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer. Nat. Med. 19, 329–336 (2013).

    Google Scholar 

  50. Gaudreault, N. N., Madden, D. W., Wilson, W. C., Trujillo, J. D. & Richt, J. A. African swine fever virus: an emerging DNA arbovirus. Front. Vet. Sci. 7, 215 (2020).

    Google Scholar 

  51. Borca, M. V. et al. ASFV-G-∆I177L as an effective oral nasal vaccine against the Eurasia strain of Africa swine fever. Viruses 13, https://doi.org/10.3390/v13050765 (2021).

  52. Bourry, O. et al. Oronasal or intramuscular immunization with a thermo-attenuated ASFV strain provides full clinical protection against Georgia 2007/1 challenge. Viruses 14, 2777 (2022).

    Google Scholar 

  53. Vlasov, M. et al. Administration routes and doses of the attenuated African swine fever virus strain PSA-1NH influence cross-protection of pigs against heterologous challenge. Animals 14, 1277 (2024).

    Google Scholar 

  54. Barbier, A. J., Jiang, A. Y., Zhang, P., Wooster, R. & Anderson, D. G. The clinical progress of mRNA vaccines and immunotherapies. Nat. Biotechnol. 40, 840–854 (2022).

    Google Scholar 

  55. Yuan, F. et al. Selection, Design, and Immunogenicity Studies of ASFV Antigens for Subunit mRNA Cocktail Vaccines with Specific Immune Response Profiles. ACS Infectious Diseases 11, 1907–1921 (2025).

    Google Scholar 

  56. Hu, X. et al. Development and efficacy of a novel mRNA cocktail for the delivery of African swine fever virus antigens and induction of immune responses. Microbiol. Spectr. 13, e02909–e02924 (2025).

    Google Scholar 

  57. Tian, C. et al. Immunogenicity and efficacy of an LNP-mRNA prepared from African swine fever virus K205R1. J. Integr. Agric 24, 4026–40333 (2024).

    Google Scholar 

  58. Diep, N. V. et al. Genotype II live-attenuated ASFV vaccine strains unable to completely protect pigs against the emerging recombinant ASFV genotype I/II strain in Vietnam. Vaccines 12, 1114 (2024).

    Google Scholar 

  59. Xie, X. et al. Influenza vaccine with consensus internal antigens as immunogens provides cross-group protection against influenza A viruses. Front. Microbiol. 10, 1630 (2019).

    Google Scholar 

  60. King, D. P. et al. Development of a TaqMan® PCR assay with internal amplification control for the detection of African swine fever virus. J. Virol. Methods 107, 53–61 (2003).

    Google Scholar 

  61. Zhao, D. et al. Replication and virulence in pigs of the first African swine fever virus isolated in China. Emerg. Microbes Infect. 8, 438–447 (2019).

    Google Scholar 

  62. Cardiff, R. D., Miller, C. H. & Munn, R. J. Manual hematoxylin and eosin staining of mouse tissue sections. Cold Spring Harb. Protoc. 2014, prot073411 (2014).

    Google Scholar 

Download references

Acknowledgements

This work was funded by National Key Research and Development Program of China (2024YFC2311100) and Prevention and Control of Emerging and Major Infectious Diseases-National Science and Technology Major Project (2025ZD01904400). The authors also acknowledge a donation from ShangFuShaFei (Shanghai) Biotechnology Co., Ltd. that supported the challenge experiments.

Author information

Author notes

  1. These authors contributed equally: Lanlan Dong, Nan Gao, Renqiang Liu.

Authors and Affiliations

  1. Institutes of Biomedical Sciences & Zhongshan Hospital, Fudan University, Shanghai, PR China

    Lanlan Dong, Kangli Cao, Ai Xia, Ziling Zhang, Xiaoyan Zhang & Jianqing Xu

  2. Shanghai Public Health Clinical Center, Fudan University, Shanghai, PR China

    Lanlan Dong, Ai Xia, Tianhan Yang, Cuisong Zhu, Chen Zhao, Xiaoyan Zhang & Jianqing Xu

  3. Department of Gastroenterology, Shanghai Institute of Pancreatic Diseases, National Key Laboratory of Immunity and Inflammation, Changhai Clinical Research Unit, Changhai Hospital, Naval Medical University, Shanghai, PR China

    Nan Gao

  4. State Key Laboratory for Animal Disease Control and Prevention, National African Swine Fever Para-reference Laboratory, National High Containment Facilities for Animal Diseases Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PR China

    Renqiang Liu & Dongming Zhao

  5. Department of Medicine, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, QC, Canada

    Xinghao Pan

  6. Quzhou Fudan Institute, Quzhou, PR China

    Jianqing Xu

Authors
  1. Lanlan Dong
    View author publications

    Search author on:PubMed Google Scholar

  2. Nan Gao
    View author publications

    Search author on:PubMed Google Scholar

  3. Renqiang Liu
    View author publications

    Search author on:PubMed Google Scholar

  4. Kangli Cao
    View author publications

    Search author on:PubMed Google Scholar

  5. Ai Xia
    View author publications

    Search author on:PubMed Google Scholar

  6. Tianhan Yang
    View author publications

    Search author on:PubMed Google Scholar

  7. Xinghao Pan
    View author publications

    Search author on:PubMed Google Scholar

  8. Cuisong Zhu
    View author publications

    Search author on:PubMed Google Scholar

  9. Ziling Zhang
    View author publications

    Search author on:PubMed Google Scholar

  10. Dongming Zhao
    View author publications

    Search author on:PubMed Google Scholar

  11. Chen Zhao
    View author publications

    Search author on:PubMed Google Scholar

  12. Xiaoyan Zhang
    View author publications

    Search author on:PubMed Google Scholar

  13. Jianqing Xu
    View author publications

    Search author on:PubMed Google Scholar

Contributions

J.X. conceptualized and supervised the research; J.X., X.Z., C.Z., D.Z., K.C., and L.D. designed the study and reviewed all data; L.D., N.G., R.L., A.X., T.Y., H.P., C.Z., and Z.Z. performed experiments; L.D., N.G., and R.L. collected and analyzed the data; L.D. drafted the manuscript; J.X., X.Z., and C.Z. revised the manuscript. L.D., N.G., and R.L. are co-first authors of this manuscript. All authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Dongming Zhao, Chen Zhao, Xiaoyan Zhang or Jianqing Xu.

Ethics declarations

Competing interests

Patent applications related to this work have been filed in China (application number: 202411253959.6) and internationally under the Patent Cooperation Treaty (application number: PCT/CN2024/117421), with J.X., X.Z., and L.D. listed as inventors. All other authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Revised supplementary information-20251004

Supplementary Arrive Essential 10 Checklist-Fudan University Xulab

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dong, L., Gao, N., Liu, R. et al. Recombinant vaccinia vectored ASFV vaccine enhances swine survival against genotype II challenge. npj Vaccines (2026). https://doi.org/10.1038/s41541-026-01377-0

Download citation

  • Received: 16 June 2025

  • Accepted: 12 January 2026

  • Published: 23 January 2026

  • DOI: https://doi.org/10.1038/s41541-026-01377-0

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Download PDF

Associated content

Collection

Veterinary Vaccines – One Health Approaches

Advertisement

Explore content

  • Research articles
  • Reviews & Analysis
  • News & Comment
  • Collections
  • Follow us on Twitter
  • Sign up for alerts
  • RSS feed

About the journal

  • Aims & Scope
  • Content types
  • Journal Information
  • About the Editors
  • Contact
  • Open Access
  • Calls for Papers
  • Editorial policies
  • Article Processing Charges
  • Journal Metrics
  • About the Partner

Publish with us

  • For Authors and Referees
  • Language editing services
  • Open access funding
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

npj Vaccines (npj Vaccines)

ISSN 2059-0105 (online)

nature.com sitemap

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2026 Springer Nature Limited

Nature Briefing Microbiology

Sign up for the Nature Briefing: Microbiology newsletter — what matters in microbiology research, free to your inbox weekly.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing: Microbiology