Cross-genotype protection of live-attenuated vaccine candidate for severe fever with thrombocytopenia syndrome virus in a ferret model

Yu, Kwang-Min; Park, Su‐Jin; Yu, Min-Ah; Kim, Young Il; Choi, Younho; Jung, Jae U.; Brennan, Benjamin; Choi, Young Ki

doi:10.1073/pnas.1914704116

Cited by 31 publications

(36 citation statements)

References 55 publications

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“…Greater than 8000 clinical cases were reported in China by the end of 2018, and greater than1000 clinical cases had been reported in other Asian countries to date with high mortality rates ranging from 5% up to 30% [ 17 ]. Unfortunately, no efficient vaccines and antiviral drugs are available hitherto [ 13 , 18 ]. Considering the profound impact on public health, the World Health Organization has listed SFTS as one of the top ten viral diseases that require urgent and in-depth research [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Antiviral RNA interference in disease vector (Asian longhorned) ticks

Zhong

Ren

et al. 2021

PLoS Pathog

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Disease vectors such as mosquitoes and ticks play a major role in the emergence and re-emergence of human and animal viral pathogens. Compared to mosquitoes, however, much less is known about the antiviral responses of ticks. Here we showed that Asian longhorned ticks (Haemaphysalis longicornis) produced predominantly 22-nucleotide virus-derived siRNAs (vsiRNAs) in response to severe fever with thrombocytopenia syndrome virus (SFTSV, an emerging tick-borne virus), Nodamura virus (NoV), or Sindbis virus (SINV) acquired by blood feeding. Notably, experimental acquisition of NoV and SINV by intrathoracic injection also initiated viral replication and triggered the production of vsiRNAs in H. longicornis. We demonstrated that a mutant NoV deficient in expressing its viral suppressor of RNAi (VSR) replicated to significantly lower levels than wildtype NoV in H. longicornis, but accumulated to higher levels after knockdown of the tick Dicer2-like protein identified by phylogeny comparison. Moreover, the expression of a panel of known animal VSRs in cis from the genome of SINV drastically enhanced the accumulation of the recombinant viruses. This study establishes a novel model for virus-vector-mouse experiments with longhorned ticks and provides the first in vivo evidence for an antiviral function of the RNAi response in ticks. Interestingly, comparing the accumulation levels of SINV recombinants expressing green fluorescent protein or SFTSV proteins identified the viral non-structural protein as a putative VSR. Elucidating the function of ticks’ antiviral RNAi pathway in vivo is critical to understand the virus-host interaction and the control of tick-borne viral pathogens.

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Section: Introductionmentioning

confidence: 99%

Antiviral RNA interference in disease vector (Asian longhorned) ticks

Zhong

Ren

et al. 2021

PLoS Pathog

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“…Both variants inhibited viral replication after post vaccination challenge and decreased most clinical signs. High genetic stability of the NSs knockout virus was observed even after six passages, demonstrating a low likelihood of reversion 138 .…”

Section: Therapeutics and Vaccines For Sftsvmentioning

confidence: 98%

“…The study of the rationally attenuated recombinant SFTSV demonstrated that two variants, a NSs knockout and a single amino-acid mutant can convey protection in a lethal ferret model 138 . Both variants inhibited viral replication after post vaccination challenge and decreased most clinical signs.…”

Section: Therapeutics and Vaccines For Sftsvmentioning

confidence: 99%

Baseline mapping of severe fever with thrombocytopenia syndrome virology, epidemiology and vaccine research and development

et al. 2020

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Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly emergent tick-borne bunyavirus first discovered in 2009 in China. SFTSV is a growing public health problem that may become more prominent owing to multiple competent tick-vectors and the expansion of human populations in areas where the vectors are found. Although tick-vectors of SFTSV are found in a wide geographic area, SFTS cases have only been reported from China, South Korea, Vietnam, and Japan. Patients with SFTS often present with high fever, leukopenia, and thrombocytopenia, and in some cases, symptoms can progress to severe outcomes, including hemorrhagic disease. Reported SFTSV case fatality rates range from ~5 to >30% depending on the region surveyed, with more severe disease reported in older individuals. Currently, treatment options for this viral infection remain mostly supportive as there are no licensed vaccines available and research is in the discovery stage. Animal models for SFTSV appear to recapitulate many facets of human disease, although none of the models mirror all clinical manifestations. There are insufficient data available on basic immunologic responses, the immune correlate(s) of protection, and the determinants of severe disease by SFTSV and related viruses. Many aspects of SFTSV virology and epidemiology are not fully understood, including a detailed understanding of the annual numbers of cases and the vertebrate host of the virus, so additional research on this disease is essential towards the development of vaccines and therapeutics.

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“…This study has fostered hope for the future design of preventive vaccines against SFTS. Moreover, Yu et al demonstrated the immunogenicity and prophylactic efficacy of attenuated recombinant SFTSV capable of triggering humoral immunity in immunized ferrets using two attenuated recombinant SFTSVs (rHB29NSsP102A and rHB2912aaNS) that contained a short 12 amino acid sequence derived from the NS open reading frame and a point mutation at position 102 that induced a proline-to-alanine substitution, respectively [ 118 ]. The study suggests that a live attenuated vaccine platform could be suitable for producing vaccine candidates against SFTSV.…”

Section: Preventionmentioning

confidence: 99%

Clinical Update of Severe Fever with Thrombocytopenia Syndrome

Seo

Kim

Yun

et al. 2021

Viruses

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Severe fever with thrombocytopenia syndrome (SFTS) is an acute febrile illness characterized by fever, leukopenia, thrombocytopenia, and gastrointestinal symptoms such as diarrhea, nausea, and vomiting resulting from infection with the SFTS virus (SFTSV). The SFTSV is transmitted to humans by tick bites, primarily from Haemaphysalis longicornis, Amblyomma testudinarium, Ixodes nipponensis, and Rhipicephalus microplus. Human-to-human transmission has also been reported. Since the first report of an SFTS patient in China, the number of patients has also been increasing. The mortality rate of patients with SFTS remains high because the disease can quickly lead to death through multiple organ failure. In particular, an average fatality rate of approximately 20% has been reported for SFTS patients, and no treatment strategy has been established. Therefore, effective antiviral agents and vaccines are required. Here, we aim to review the epidemiology, clinical manifestations, laboratory diagnosis, and various specific treatments (i.e., antiviral agents, steroids, intravenous immunoglobulin, and plasma exchange) that have been tested to help to cope with the disease.

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Cross-genotype protection of live-attenuated vaccine candidate for severe fever with thrombocytopenia syndrome virus in a ferret model

Cited by 31 publications

References 55 publications

Antiviral RNA interference in disease vector (Asian longhorned) ticks

Antiviral RNA interference in disease vector (Asian longhorned) ticks

Baseline mapping of severe fever with thrombocytopenia syndrome virology, epidemiology and vaccine research and development

Clinical Update of Severe Fever with Thrombocytopenia Syndrome

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