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Full text release has been delayed at the author's request until May 17, 2026

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Development of SFTSV Gn Head-Ferritin Nanoparticle and mRNA Vaccine & Repurposing the Nanoparticle Vaccine for Preventive and Therapeutic Medicine

Kim, Dokyun
http://orcid.org/0000-0002-3284-7623
http://rave.ohiolink.edu/etdc/view?acc_num=case1706105114583644

Abstract Details

2024, Doctor of Philosophy, Case Western Reserve University, Molecular Medicine.
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus causing hemorrhagic fever with mortality rate ranging up to 30%. However, licensed vaccine or targeted therapy against SFTSV is yet to be developed. In this study, we developed a protein subunit vaccine employing 24-mer self-assembling ferritin (FT) nanoparticles as a platform to present the head region of the SFTSV Gn (GnH). The purified GnH-FT nanoparticles preserved structural integrity and induced robust humoral and cellular immunity against SFTSV Gn. Furthermore, aged ferrets that received immunization with GnH-FT nanoparticles exhibited complete protection from lethal SFTSV challenge and symptoms of body weight loss, viremia, fever, thrombocytopenia, leukopenia, and mortality. We also developed mRNA vaccines encoding GnH and GnH-FT, which potently induce immunity against SFTSV and provides full protection against lethal SFTSV infection in mouse model. Furthermore, we repurposed the GnH-FT nanoparticle to develop therapeutic antibody against SFTSV. We identified five unique antibodies specifically binding SFTSV, including two candidates with sub-nanomolar KD. Our study suggests two vaccine candidates and potential therapeutic antibodies against SFTSV.
Jae Jung (Advisor)
Feixiong Cheng (Committee Chair)
Xinghong Dai (Committee Member)
Christine O'Connor (Committee Member)
Jun Qin (Committee Member)
Frank Esper (Committee Member)
170 p.
Immunology; Microbiology; Virology
Nanoparticle Vaccine, Subunit Vaccine, mRNA Vaccine, Therapeutic Antibody, Nanobody, Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV)

Recommended Citations

Citations

  • Kim, D. (2024). Development of SFTSV Gn Head-Ferritin Nanoparticle and mRNA Vaccine & Repurposing the Nanoparticle Vaccine for Preventive and Therapeutic Medicine [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1706105114583644

    APA Style (7th edition)

  • Kim, Dokyun. Development of SFTSV Gn Head-Ferritin Nanoparticle and mRNA Vaccine & Repurposing the Nanoparticle Vaccine for Preventive and Therapeutic Medicine. 2024. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1706105114583644.

    MLA Style (8th edition)

  • Kim, Dokyun. "Development of SFTSV Gn Head-Ferritin Nanoparticle and mRNA Vaccine & Repurposing the Nanoparticle Vaccine for Preventive and Therapeutic Medicine." Doctoral dissertation, Case Western Reserve University, 2024. http://rave.ohiolink.edu/etdc/view?acc_num=case1706105114583644

    Chicago Manual of Style (17th edition)

case1706105114583644
© 2024, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.