Skip to main content
Log in

Vaccine Development for Severe Fever with Thrombocytopenia Syndrome Virus in Dogs

  • Virology
  • Published:
Journal of Microbiology Aims and scope Submit manuscript

Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening viral zoonosis. The causative agent of this disease is the Dabie bandavirus, which is usually known as the SFTS virus (SFTSV). Although the role of vertebrates in SFTSV transmission to humans remains uncertain, some reports have suggested that dogs could potentially transmit SFTSV to humans. Consequently, preventive measures against SFTSV in dogs are urgently needed. In the present study, dogs were immunized three times at two-week intervals with formaldehyde-inactivated SFTSV with two types of adjuvants. SFTSV (KCD46) was injected into all dogs two weeks after the final immunization. Control dogs showed viremia from 2 to 4 days post infection (dpi), and displayed white pulp atrophy in the spleen, along with a high level of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay (TUNEL) positive area. However, the inactivated SFTSV vaccine groups exhibited rare pathological changes and significantly reduced TUNEL positive areas in the spleen. Furthermore, SFTSV viral loads were not detected at any of the tested dpi. Our results indicate that both adjuvants can be safely used in combination with an inactivated SFTSV formulation to induce strong neutralizing antibodies. Inactivated SFTSV vaccines effectively prevent pathogenicity and viremia in dogs infected with SFTSV. In conclusion, our study highlighted the potential of inactivated SFTSV vaccination for SFTSV control in dogs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data Availability

All data supporting the findings of the present study are available upon reasonable request from the corresponding author.

References

  • AboulFotouh, K., Uno, N., Xu, H., Moon, C., Sahakijpijarn, S., Christensen, D. J., Davenport, G. J., Cano, C., Ross, T. M., Williams Iii, R. O., et al. (2022). Formulation of dry powders of vaccines containing MF59 or AddaVax by thin-film freeze-drying: Towards a dry powder universal flu vaccine. International Journal of Pharmaceutics, 624, 122021.

    Article  CAS  PubMed  Google Scholar 

  • Ando, T., Nabeshima, T., Inoue, S., Tun, M. M. N., Obata, M., Hu, W., Shimoda, H., Kurihara, S., Izumikawa, K., Morita, K., et al. (2021). Severe fever with thrombocytopenia syndrome in cats and its prevalence among veterinarian staff members in Nagasaki Japan. Viruses, 13, 1142.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Casel, M. A., Park, S. J., & Choi, Y. K. (2021). Severe fever with thrombocytopenia syndrome virus: Emerging novel phlebovirus and their control strategy. Experimental & Molecular Medicine, 53, 713–722.

    Article  CAS  Google Scholar 

  • Chen, C., Li, P., Li, K. F., Wang, H. L., Dai, Y. X., Cheng, X., & Yan, J. B. (2019). Animals as amplification hosts in the spread of severe fever with thrombocytopenia syndrome virus: A systematic review and meta-analysis. International Journal of Infectious Diseases, 79, 77–84.

    Article  PubMed  Google Scholar 

  • Chung, J. K., Kim, C. M., Kim, D. M., Yun, N. R., Park, J. W., Seo, J., & Kim, Y. S. (2020). Severe fever with thrombocytopenia syndrome associated with manual de-ticking of domestic dogs. Vector-Borne and Zoonotic Diseases, 20, 285–294.

    Article  PubMed  Google Scholar 

  • Decaro, N., Mari, V., Sciarretta, R., Colao, V., Losurdo, M., Catella, C., Elia, G., Martella, V., Giudice, G. D., & Buonavoglia, C. (2011). Immunogenicity and protective efficacy in dogs of an MF59™-adjuvanted vaccine against recombinant canine/porcine coronavirus. Vaccine, 29, 2018–2023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fan, J., Jin, S., Gilmartin, L., Toth, I., Hussein, W. M., & Stephenson, R. J. (2022). Advances in infectious disease vaccine adjuvants. Vaccines, 10, 1120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fang, L., Yu, S., Tian, X., Fu, W., Su, L., Chen, Z., Yan, C., He, J., Hong, J., Lian, W., et al. (2023). Severe fever with thrombocytopenia syndrome virus replicates in platelets and enhances platelet activation. Journal of Thrombosis and Haemostasis, 21, 1336–1351.

    Article  PubMed  Google Scholar 

  • Gai, Z. T., Zhang, Y., Liang, M. F., Jin, C., Zhang, S., Zhu, C. B., Li, C., Li, X. Y., Zhang, Q. F., Bian, P. F., et al. (2012). Clinical progress and risk factors for death in severe fever with thrombocytopenia syndrome patients. Journal of Infectious Diseases, 206, 1095–1102.

    Article  CAS  PubMed  Google Scholar 

  • Golding, H., Khurana, S., & Zaitseva, M. (2018). What is the predictive value of animal models for vaccine efficacy in humans? The importance of bridging studies and species-independent correlates of protection. Cold Spring Harbor Perspectives in Biology, 10, a028902.

    Article  PubMed  PubMed Central  Google Scholar 

  • Han, S. W., Kang, J. G., Byeon, A. R., Cho, Y. K., Choi, K. S., & Chae, J. S. (2020). Severe fever with thrombocytopenia syndrome in canines from the Republic of Korea. Ticks and Tick-Borne Disease, 11, 101454.

    Article  Google Scholar 

  • Ishijima, K., Tatemoto, K., Park, E., Kimura, M., Fujita, O., Taira, M., Kuroda, Y., Mendoza, M. V., Inoue, Y., Harada, M., et al. (2022). Lethal disease in dogs naturally infected with severe fever with thrombocytopenia syndrome virus. Viruses, 14, 1963.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kang, J. G., Cho, Y. K., Jo, Y. S., Chae, J. B., Joo, Y. H., Park, K. W., & Chae, J. S. (2019). Severe fever with thrombocytopenia syndrome virus in dogs, South Korea. Emerging Infectious Diseases, 25, 376–378.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kang, J. G., Cho, Y. K., Jo, Y. S., Han, S. W., Chae, J. B., Park, J. E., Jeong, H., Jheong, W. H., & Chae, J. S. (2022). Severe Fever with thrombocytopenia syndrome virus in ticks in the Republic of Korea. The Korean Journal of Parasitology, 60, 65–71.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kang, J. G., Jeon, K., Choi, H., Kim, Y., Kim, H. I., Ro, H. J., Seo, Y. B., Shin, J., Chung, J., Jeon, Y. K., et al. (2020). Vaccination with single plasmid DNA encoding IL-12 and antigens of severe fever with thrombocytopenia syndrome virus elicits complete protection in IFNAR knockout mice. PLoS Neglected Tropical Diseases, 14, e0007813.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim, W. Y., Choi, W. Y., Park, S. W., Wang, E. B., Lee, W. J., Jee, Y., Lim, K. S., Lee, H. J., Kim, S. M., Lee, S. O., et al. (2015). Nosocomial transmission of severe fever with thrombocytopenia syndrome in Korea. Clinical Infectious Diseases, 60, 1681–1683.

    Article  CAS  PubMed  Google Scholar 

  • Kim, J. W., Yang, D., Jeong, H., Park, I. S., Lee, M. H., Lim, C. W., & Kim, B. (2019). Dietary zerumbone, a sesquiterpene, ameliorates hepatotoxin-mediated acute and chronic liver injury in mice. Phytotherapy Research, 33, 1538–1550.

    Article  CAS  PubMed  Google Scholar 

  • Kwak, J. E., Kim, Y. I., Park, S. J., Yu, M. A., Kwon, H. I., Eo, S., Kim, T. S., Seok, J., Choi, W. S., Jeong, J. H., et al. (2019). Development of a SFTSV DNA vaccine that confers complete protection against lethal infection in ferrets. Nature Communications, 10, 3836.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee, D. H., Bae, S. W., Park, J. K., Kwon, J. H., Yuk, S. S., Song, J. M., Kang, S. M., Kwon, Y. K., Kim, H. Y., & Song, C. S. (2013). Virus-like particle vaccine protects against H3N2 canine influenza virus in dog. Vaccine, 31, 3268–3273.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li, A., Dai, X., Chen, L., Liu, L., Li, C., Liu, Y., Wu, W., Huang, X., Li, J., Wang, S., et al. (2022). Immunogenicity and protective efficacy of an inactivated SFTS vaccine candidate in mice. Biosafety and Health, 4, 45–52.

    Article  Google Scholar 

  • Luo, L. M., Zhao, L., Wen, H. L., Zhang, Z. T., Liu, J. W., Fang, L. Z., Xue, Z. F., Ma, D. Q., Zhang, X. S., Ding, S. J., et al. (2015). Haemaphysalis longicornis ticks as reservoir and vector of severe fever with thrombocytopenia syndrome virus in China. Emerging Infectious Diseases, 21, 1770–1776.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagashima, K., Abbadi, N., Vyas, V., Roegner, A., Ross, T. M., & Mousa, J. J. (2023). Adjuvant-mediated differences in antibody responses to computationally optimized hemagglutinin and neuraminidase vaccines. Viruses, 15, 347.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nam, S. J., Oh, Y. I., Kim, H. J., Cheon, D. S., Noh, S. J., & Hong, Y. J. (2020). Unusual case of severe fever with thrombocytopenia syndrome showing clinical manifestations in a companion dog. Veterinary Medicine and Science, 6, 353–358.

    Article  PubMed  PubMed Central  Google Scholar 

  • O’Hagan, D. T., Ott, G. S., De Gregorio, E., & Seubert, A. (2011). The mechanism of action of MF59–an innately attractive adjuvant formulation. Vaccine, 30, 4341–4348.

    Article  Google Scholar 

  • Oshima, H., Okumura, H., Maeda, K., Ishijima, K., Yoshikawa, T., Kurosu, T., Fukushi, S., Shimojima, M., & Saijo, M. (2022). A patient with severe fever with thrombocytopenia syndrome (SFTS) infected from a sick dog with SFTS virus infection. Japanese Journal of Infectious Diseases, 75, 423–426.

    Article  CAS  PubMed  Google Scholar 

  • Park, S. J., Kim, Y. I., Park, A., Kwon, H. I., Kim, E. H., Si, Y. J., Song, M. S., Lee, C. H., Jung, K., Shin, W. J., et al. (2019). Ferret animal model of severe fever with thrombocytopenia syndrome phlebovirus for human lethal infection and pathogenesis. Nature Microbiology, 4, 438–446.

    Article  CAS  PubMed  Google Scholar 

  • Park, S. C., Park, J. Y., Choi, J. Y., Lee, S. G., Eo, S. K., Oem, J. K., Tark, D. S., You, M., Yu, D. H., Chae, J. S., et al. (2020). Pathogenicity of severe fever with thrombocytopenia syndrome virus in mice regulated in type I interferon signaling. Laboratory Animal Research, 36, 38.

    Article  PubMed  PubMed Central  Google Scholar 

  • Park, S. C., Park, J. Y., Choi, J. Y., Oh, B., Yang, M. S., Lee, S. Y., Kim, J. W., Eo, S. K., Chae, J. S., Lim, C. W., et al. (2022). Experimental infection of dogs with severe fever with thrombocytopenia syndrome virus: Pathogenicity and potential for intraspecies transmission. Transboundary and Emerging Diseases, 69, 3090–3096.

    Article  CAS  PubMed  Google Scholar 

  • Shi, S., Zhu, H., Xia, X., Liang, Z., Ma, X., & Sun, B. (2019). Vaccine adjuvants: Understanding the structure and mechanism of adjuvanticity. Vaccine, 37, 3167–3178.

    Article  CAS  PubMed  Google Scholar 

  • Spickler, A. R., & Roth, J. A. (2003). Adjuvants in veterinary vaccines: Modes of action and adverse effects. Journal of Veterinary Internal Medicine, 17, 273–281.

    Article  PubMed  Google Scholar 

  • Tang, X., Wu, W., Wang, H., Du, Y., Liu, L., Kang, K., Huang, X., Ma, H., Mu, F., Zhang, S., et al. (2013). Human-to-human transmission of severe fever with thrombocytopenia syndrome bunyavirus through contact with infectious blood. The Journal of Infectious Diseases, 207, 736–739.

    Article  PubMed  Google Scholar 

  • Tsuru, M., Suzuki, T., Murakami, T., Matsui, K., Maeda, Y., Yoshikawa, T., Kurosu, T., Shimojima, M., Shimada, T., Hasegawa, H., et al. (2021). Pathological characteristics of a patient with severe fever with thrombocytopenia syndrome (SFTS) infected with SFTS virus through a sick cat’s bite. Viruses, 13, 204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Villarreal, R., & Casale, T. B. (2020). Commonly used adjuvant human vaccines: Advantages and side effects. The Journal of Allergy and Clinical Immunology. In Practice, 8, 2953–2957.

    PubMed  Google Scholar 

  • Watanabe, T., Horikawa, Y., Sato, K., & Saito, H. (1982). Methylcellulose media for plaque assay of murine leukemia virus. Journal of Clinical Microbiology, 16, 542–544.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye, C., & Qi, R. (2021). Risk factors for person-to-person transmission of severe fever with thrombocytopenia syndrome. Infection Control & Hospital Epidemiology, 42, 582–585.

    Article  Google Scholar 

  • Yoshikawa, T., Taniguchi, S., Kato, H., Iwata-Yoshikawa, N., Tani, H., Kurosu, T., Fujii, H., Omura, N., Shibamura, M., Watanabe, S., et al. (2021). A highly attenuated vaccinia virus strain LC16m8-based vaccine for severe fever with thrombocytopenia syndrome. PLoS Pathogens, 17, e1008859.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu, X. J., Liang, M. F., Zhang, S. Y., Liu, Y., Li, J. D., Sun, Y. L., Zhang, L., Zhang, Q. F., Popov, V. L., Li, C., et al. (2011). Fever with thrombocytopenia associated with a novel bunyavirus in China. New England Journal of Medicine, 364, 1523–1532.

    Article  CAS  PubMed  Google Scholar 

  • Zhao, Z., Zheng, W., Yan, L., Sun, P., Xu, T., Zhu, Y., Liu, L., Tian, L., He, H., Wei, Y., et al. (2020). Recombinant human adenovirus type 5 co-expressing RABV G and SFTSV Gn induces protective immunity against rabies virus and severe fever with thrombocytopenia syndrome virus in mice. Frontiers in Microbiology, 11, 1473.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zu, Z., Lin, H., Hu, Y., Zheng, X., Chen, C., Zhao, Y., Zhang, Z., & He, N. (2024). Seroprevalence and transmission of severe fever with thrombocytopenia syndrome virus in a coastal endemic area in Southeastern China. Ticks and Tick-Borne Diseases, 15, 102277.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, and Forestry (IPET) through the Animal Disease Management Technology Development Program funded by the Ministry of Agriculture, Food, and Rural Affairs (MAFRA) [321014-01].

Author information

Authors and Affiliations

Authors

Contributions

JGK conceived the study and designed the experiments. SCP and JGK prepared the manuscript. SCP, DEJ, SWH, JYL, and HSK carried out animal experiments, sample collection, and sample analysis. JSC, BK, and JGK provided significant intellectual input and revised the manuscript. All the authors have read and approved the final version of the manuscript.

Corresponding author

Correspondence to Jun-Gu Kang.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, SC., Jeong, DE., Han, SW. et al. Vaccine Development for Severe Fever with Thrombocytopenia Syndrome Virus in Dogs. J Microbiol. (2024). https://doi.org/10.1007/s12275-024-00119-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12275-024-00119-y

Keywords

Navigation