Development of a SFTSV DNA vaccine that confers complete protection against lethal infection in ferrets

Jeong Eun Kwak; Young Il Kim; Su Jin Park; Min Ah Yu; Hyeok Il Kwon; Sukyeong Eo; Tae Shin Kim; Joon Seok; Won Suk Choi; Ju Hwan Jeong; Hyojin Lee; Youngran Cho; Jin Ah Kwon; Moonsup Jeong; Joel N. Maslow; Yong Eun Kim; Haili Jeon; Kee K. Kim; Eui Cheol Shin; Min Suk Song; Jae U. Jung; Young Ki Choi; Su Hyung Park

doi:10.1038/s41467-019-11815-4

Development of a SFTSV DNA vaccine that confers complete protection against lethal infection in ferrets

Jeong Eun Kwak, Young Il Kim, Su Jin Park, Min Ah Yu, Hyeok Il Kwon, Sukyeong Eo, Tae Shin Kim, Joon Seok, Won Suk Choi, Ju Hwan Jeong, Hyojin Lee, Youngran Cho, Jin Ah Kwon, Moonsup Jeong, Joel N. Maslow, Yong Eun Kim, Haili Jeon, Kee K. Kim, Eui Cheol Shin, Min Suk SongJae U. Jung, Young Ki Choi, Su Hyung Park

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Abstract

Although the incidence of severe fever with thrombocytopenia syndrome virus (SFTSV) infection has increased from its discovery with a mortality rate of 10–20%, no effective vaccines are currently available. Here we describe the development of a SFTSV DNA vaccine, its immunogenicity, and its protective efficacy. Vaccine candidates induce both a neutralizing antibody response and multifunctional SFTSV-specific T cell response in mice and ferrets. When the vaccine efficacy is investigated in aged-ferrets that recapitulate fatal clinical symptoms, vaccinated ferrets are completely protected from lethal SFTSV challenge without developing any clinical signs. A serum transfer study reveals that anti-envelope antibodies play an important role in protective immunity. Our results suggest that Gn/Gc may be the most effective antigens for inducing protective immunity and non-envelope-specific T cell responses also can contribute to protection against SFTSV infection. This study provides important insights into the development of an effective vaccine, as well as corresponding immune parameters, to control SFTSV infection.

Original language	English (US)
Article number	3836
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-11815-4
State	Published - Dec 1 2019

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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10.1038/s41467-019-11815-4

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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., Lee, H., Cho, Y., Kwon, J. A., Jeong, M., Maslow, J. N., Kim, Y. E., Jeon, H., Kim, K. K., Shin, E. C., ... Park, S. H. (2019). Development of a SFTSV DNA vaccine that confers complete protection against lethal infection in ferrets. Nature Communications, 10(1), Article 3836. https://doi.org/10.1038/s41467-019-11815-4

Kwak, JE, Kim, YI, Park, SJ, Yu, MA, Kwon, HI, Eo, S, Kim, TS, Seok, J, Choi, WS, Jeong, JH, Lee, H, Cho, Y, Kwon, JA, Jeong, M, Maslow, JN, Kim, YE, Jeon, H, Kim, KK, Shin, EC, Song, MS, Jung, JU, Choi, YK & Park, SH 2019, 'Development of a SFTSV DNA vaccine that confers complete protection against lethal infection in ferrets', Nature Communications, vol. 10, no. 1, 3836. https://doi.org/10.1038/s41467-019-11815-4

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title = "Development of a SFTSV DNA vaccine that confers complete protection against lethal infection in ferrets",

abstract = "Although the incidence of severe fever with thrombocytopenia syndrome virus (SFTSV) infection has increased from its discovery with a mortality rate of 10–20%, no effective vaccines are currently available. Here we describe the development of a SFTSV DNA vaccine, its immunogenicity, and its protective efficacy. Vaccine candidates induce both a neutralizing antibody response and multifunctional SFTSV-specific T cell response in mice and ferrets. When the vaccine efficacy is investigated in aged-ferrets that recapitulate fatal clinical symptoms, vaccinated ferrets are completely protected from lethal SFTSV challenge without developing any clinical signs. A serum transfer study reveals that anti-envelope antibodies play an important role in protective immunity. Our results suggest that Gn/Gc may be the most effective antigens for inducing protective immunity and non-envelope-specific T cell responses also can contribute to protection against SFTSV infection. This study provides important insights into the development of an effective vaccine, as well as corresponding immune parameters, to control SFTSV infection.",

author = "Kwak, {Jeong Eun} and Kim, {Young Il} and Park, {Su Jin} and Yu, {Min Ah} and Kwon, {Hyeok Il} and Sukyeong Eo and Kim, {Tae Shin} and Joon Seok and Choi, {Won Suk} and Jeong, {Ju Hwan} and Hyojin Lee and Youngran Cho and Kwon, {Jin Ah} and Moonsup Jeong and Maslow, {Joel N.} and Kim, {Yong Eun} and Haili Jeon and Kim, {Kee K.} and Shin, {Eui Cheol} and Song, {Min Suk} and Jung, {Jae U.} and Choi, {Young Ki} and Park, {Su Hyung}",

note = "Funding Information: This work was supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI15C2888 to S.H.P. and HI15C2817 to Y.K.C. and S.H.P.) and a grant from Government-wide R&D Fund project for infectious disease research, Republic of Korea (HG18C0029 to Y.K.C.). This work was also supported by a Global Ph.D. Fellowship from the National Research Foundation of Korea (NRF-2017H1A2A1046321 to J.E.K.). Publisher Copyright: {\textcopyright} 2019, The Author(s).",

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AU - Kwak, Jeong Eun

AU - Kim, Young Il

AU - Park, Su Jin

AU - Yu, Min Ah

AU - Kwon, Hyeok Il

AU - Eo, Sukyeong

AU - Kim, Tae Shin

AU - Seok, Joon

AU - Choi, Won Suk

AU - Jeong, Ju Hwan

AU - Lee, Hyojin

AU - Cho, Youngran

AU - Kwon, Jin Ah

AU - Jeong, Moonsup

AU - Maslow, Joel N.

AU - Kim, Yong Eun

AU - Jeon, Haili

AU - Kim, Kee K.

AU - Shin, Eui Cheol

AU - Song, Min Suk

AU - Jung, Jae U.

AU - Choi, Young Ki

AU - Park, Su Hyung

N1 - Funding Information: This work was supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI15C2888 to S.H.P. and HI15C2817 to Y.K.C. and S.H.P.) and a grant from Government-wide R&D Fund project for infectious disease research, Republic of Korea (HG18C0029 to Y.K.C.). This work was also supported by a Global Ph.D. Fellowship from the National Research Foundation of Korea (NRF-2017H1A2A1046321 to J.E.K.). Publisher Copyright: © 2019, The Author(s).

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Although the incidence of severe fever with thrombocytopenia syndrome virus (SFTSV) infection has increased from its discovery with a mortality rate of 10–20%, no effective vaccines are currently available. Here we describe the development of a SFTSV DNA vaccine, its immunogenicity, and its protective efficacy. Vaccine candidates induce both a neutralizing antibody response and multifunctional SFTSV-specific T cell response in mice and ferrets. When the vaccine efficacy is investigated in aged-ferrets that recapitulate fatal clinical symptoms, vaccinated ferrets are completely protected from lethal SFTSV challenge without developing any clinical signs. A serum transfer study reveals that anti-envelope antibodies play an important role in protective immunity. Our results suggest that Gn/Gc may be the most effective antigens for inducing protective immunity and non-envelope-specific T cell responses also can contribute to protection against SFTSV infection. This study provides important insights into the development of an effective vaccine, as well as corresponding immune parameters, to control SFTSV infection.

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Development of a SFTSV DNA vaccine that confers complete protection against lethal infection in ferrets

Abstract

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