Current Progress of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) Vaccine Development
Abstract
:1. Introduction
2. SFTSV Biology
3. Animal Models to Study Efficacy of SFTSV Vaccines
3.1. Newborn Mouse
3.2. Type I interferon Receptor (IFNAR) KO Mouse
3.3. WT Mouse Treated with IFNAR-Neutralizing Antibody (IFNAR-NAb)
3.4. Non-Human Primates (NHP)
3.5. Aged Ferret
4. Types of SFTSV Vaccines Developed to Date
4.1. Live-Attenuated Vaccine Platform
4.2. DNA Vaccine Platform
4.2.1. DNA Vaccine Encoding Gn/Gc
4.2.2. DNA Vaccine Encoding Gn/Gc and Mouse IL-12 (mIL-12)
4.3. Whole Inactivated Viral Vaccine Platform
4.4. Viral Vector Vaccine Platform
4.4.1. Recombinant Vesicular Stomatitis Virus (rVSV)-Vectored Vaccine
4.4.2. Recombinant Vaccinia Virus (rVACV)-Vectored Vaccine
4.5. Protein Subunit Vaccine Platform
4.5.1. Recombinant NSs Protein with Complete Freund’s Adjuvant (CFA)
4.5.2. Gn and Gc-Fc
4.5.3. Self-Assembling Gn Head-Ferritin Nanoparticle Vaccine
4.6. Heterologous Vaccination
4.7. mRNA Vaccine Platform
Viral Antigen | Carrier/Adjuvant | Dose | Immunization Schedule | Animal Model Used | Viral Challenge | Efficacy | Advantage | Disadvantages | Reference | |
---|---|---|---|---|---|---|---|---|---|---|
Live-attenuated vaccine | Truncation mutant of NSs | - | 4 × 106 pfu (rHB2912aaNSs) | Single immunization | Aged ferrets | 107.6 TCID50 | Full protection from BW loss, fever, serum viremia, fatality | Potent immunogenicity | Concern of reversion mutation and side effect from potentially excessive immunogenicity | [111] |
Substitution mutant of NSs | 5 × 105 pfu (rHB29NSsP102A) | |||||||||
DNA vaccine | Gn/Gc | 40 μg | Weeks 0, 3 | Aged ferrets Immunized & serum-transferred | 107.6 TCID50, 2 or 4 weeks after the last immunization | Full protection from both immunized & serum-transferred ferrets BW loss, fever, thrombocytopenia, leukopenia, viremia, and fatality | Low cost of production | Concern of genome integration Electroporator required for immunization | [112] | |
Gn/Gc, RdRp, N, and NSs | - | 4 μg | Weeks 0, 2, 4 | IFNAR KO mice | 1 × 105 ffu 2 weeks after the last immunization | 40% fatality and severe BW loss, thrombocytopenia, and viremia | [113] | |||
Gn, Gc, RdRp, N, and NSs | Mouse IL-12 | Full protection from BW loss, thrombocytopenia, serum viremia, and fatality | ||||||||
Whole inactivated vaccine | Inactivated whole virion | Al(OH)3 adjuvant | Glycoproteins of 0.25, 1, or 4 μg | Weeks 0, 2, 4 | Wild type C57BL/6 | 105 TCID50 2 weeks after the last immunization | Accelerated viral clearance (WT C57BL/6 does not develop SFTS) | Balanced B & T cell activation Replicates natural infection | Logistic difficulty of large culture of BSL-3 agent (SFTSV) | [114] |
Viral vectored vaccine | Gn/Gc | rVSV | 2 × 104 pfu | Single immunization | IFNAR KO mice | 2 × 104 ffu 30 days after the last immunization | Full protection from BW loss, viremia, and fatality | Strong induction of B and T cell & Ease of mass production | Potential risk of side effects | [118] |
Gn/Gc | rVACV (from m8 strain) | 1 × 106 pfu | Weeks 0, 2 | IFNAR KO mice | 1 × 103 and 1 × 105 TCID50 2 weeks after the last immunization | Full protection from BW loss and fatality | Reduced immunogenicity from pre-existing immunity | [124] | ||
Protein subunit vaccine | NSs | Complete Freund’s adjuvant | 100 μg | Weeks 0, 2 | Wild type C57BL/6 | 3 × 107 pfu 12 days after the last immunization | Failed to accelerate viral clearance (WT C57BL/6 does not develop SFTS) | Higher safety profile for the elderly population | Failed to provide immunity | [131] |
Gn | Human Fc & Alum adjuvant | 20 μg | Weeks 0, 2 | IFNAR KO mice | 1 × 105 ffu 2 weeks after the last immunization | 50% fatality and severe BW loss | Failed to provide sufficient immunity | [113] | ||
Gc | 100% fatality and severe BW loss | Failed to provide immunity | ||||||||
Gn (head region) | Ferritin nanoparticle & AddaVax adjuvant | 15 μg | Weeks 0, 2, 4 | Aged ferrets | 1 × 107.6 TCID50 2 weeks after the last immunization | Full protection from BW loss, fever, thrombocytopenia, leukopenia, viremia, and fatality | Cost of production | [132] | ||
Heterologous vaccine | Gn (head region & head + stem region) | rAd5 + CrPV & Al(OH)3 adjuvant | rAd5-Gn/Gn: 1 × 109 IU rAd5-Gn, then 5 μg Gn | Weeks 0, 2 | Wild type C57BL/6 injected with IFNAR-NAb and IL-10 | 1 × 105 ffu 3 weeks after the last immunization | Full protection from BW loss, splenomegaly, liver damage, and viremia | rAd5-Gn reduces cost of production | Complicated immunization protocol | [139] |
Gn/rAd5-Gn: 5 μg Gn, then 1 × 109 IU rAd5-Gn | ||||||||||
mRNA vaccine | Gn (head region) | lipid nanoparticle | 3 μg | Weeks 0, 3 | IFNAR KO mice | 2 × 104 pfu 2 weeks after the last immunization | Full protection from BW loss and fatliaty | Low cost & rapid production | Cold chain supply required | [144] |
Gn (head region) | Ferritin & lipid nanoparticle |
5. Conclusions and Future Directions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Kim, D.; Lai, C.-J.; Cha, I.; Jung, J.U. Current Progress of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) Vaccine Development. Viruses 2024, 16, 128. https://doi.org/10.3390/v16010128
Kim D, Lai C-J, Cha I, Jung JU. Current Progress of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) Vaccine Development. Viruses. 2024; 16(1):128. https://doi.org/10.3390/v16010128
Chicago/Turabian StyleKim, Dokyun, Chih-Jen Lai, Inho Cha, and Jae U. Jung. 2024. "Current Progress of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) Vaccine Development" Viruses 16, no. 1: 128. https://doi.org/10.3390/v16010128