Single dose of a rVSV-based vaccine elicits complete protection against severe fever with thrombocytopenia syndrome virus

Dong, Fangfang; Li, Dandan; Wen, Dan; Li, Suhua; Zhao, Chaoyue; Qi, Yue; Jangra, Rohit K.; Wu, Chunyan; Xia, De-quan; Zhang, Xing; Deng, Fei; Chandran, Kartik; Zou, Zhen; Yuan, Fei; Zheng, Aihua

doi:10.1038/s41541-018-0096-y

Cited by 53 publications

(66 citation statements)

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“…In addition, the fact that recombinants can be manufactured quickly with diverse antigens further adds to its value as a vaccine platform for outbreak pathogens. While we have focused here on WHO blueprint priority pathogens, a variety of VSV-based vaccine candidates have been described for other emerging or reemerging pathogens, including enterovirus 71, 126 Chikungunya, 127,128 West-Nile, 129 Dengue,130 Severe fever with thrombocytopenia syndrome, 131 and Andes viruses. [132][133][134] Animal studies of VSV-based vector vaccines against MARV, LASV, NiV, ZIKV, and MERS-and SARS-CoV described above have yielded promising results and the progression of rVSV vaccine candidates to clinical trials may add to the portfolio of effective outbreak vaccines in the foreseeable future.…”

Section: Resultsmentioning

confidence: 99%

Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens

Fathi

Dahlke

Addo

2019

Human Vaccines & Immunotherapeutics

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The devastating Ebola virus (EBOV) outbreak in West Africa in 2013-2016 has flagged the need for the timely development of vaccines for high-threat pathogens. To be better prepared for new epidemics, the WHO has compiled a list of priority pathogens that are likely to cause future outbreaks and for which R&D efforts are, therefore, paramount (R&D Blueprint: https://www.who.int/blueprint/priority-diseases/en/). To this end, the detailed characterization of vaccine platforms is needed. The vesicular stomatitis virus (VSV) has been established as a robust vaccine vector backbone for infectious diseases for well over a decade. The recent clinical trials testing the vaccine candidate VSV-EBOV against EBOV disease now have added a substantial amount of clinical data and suggest VSV to be an ideal vaccine vector candidate for outbreak pathogens. In this review, we discuss insights gained from the clinical VSV-EBOV vaccine trials as well as from animal studies investigating vaccine candidates for Blueprint pathogens. ARTICLE HISTORY

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Section: Resultsmentioning

confidence: 99%

Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens

Fathi

Dahlke

Addo

2019

Human Vaccines & Immunotherapeutics

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Section: Discussionmentioning

confidence: 99%

“…There are two studies for developing vaccines against SFTSV infection (Dong et al, 2019;Kwak et al, 2019). A recombinant vesicular stomatitis virus expressing SFTSV antigen completely protected mice from SFTSV infection (Dong et al, 2019). A DNA vaccine expressing antigens of SFTSV, elicited both neutralizing antibody response and SFTSV-specific T cell response and protected aged-ferrets from the lethal SFTSV infection (Kwak et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

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Antiviral Drugs Against Severe Fever With Thrombocytopenia Syndrome Virus Infection

Takayama-Ito

Saijo

2020

Front. Microbiol.

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Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by SFTS virus (SFTSV), which is a novel bunyavirus. SFTSV was first isolated from patients who presented with fever, thrombocytopenia, leukocytopenia, and multiorgan dysfunction in China. Subsequently, it was found to be widely distributed in Southeast Asia (Korea, Japan, and Vietnam). SFTSV can be transmitted not only from ticks but also from domestic animals, companion animals, and humans. Because the case fatality rate of SFTS is high (6-30%), development of specific and effective treatment for SFTS is required. Studies of potential antiviral drugs for SFTS-specific therapy have been conducted on existing or newly discovered agents in vitro and in vivo, with ribavirin and favipiravir being the most promising candidates. While animal experiments and retrospective studies have demonstrated the limited efficacy of ribavirin, it was also speculated that ribavirin would be effective in patients with a viral load <1 × 10 6 copies/mL. Favipiravir showed higher efficacy than ribavirin against SFTSV in in vitro assays and greater efficacy in animal models, even administrated 3 days after the virus inoculation. Although clinical trials evaluating the efficacy of favipiravir in SFTS patients in Japan are underway, this has yet to be confirmed. Other drugs, including hexachlorophene, calcium channel blockers, 2 ′ -fluoro-2 ′ -deoxycytidine, caffeic acid, amodiaquine, and interferons, have also been evaluated for their inhibitory efficacy against SFTSV. Among them, calcium channel blockers are promising because in addition to their efficacy in vitro and in vivo, retrospective clinical data have indicated that nifedipine, one of the calcium channel blockers, reduced the case fatality rate by >5-fold. Although further research is necessary to develop SFTS-specific therapy, considerable progress has been achieved in this area. Here we summarize and discuss recent advances in antiviral drugs against SFTSV.Keywords: severe fever with thrombocytopenia syndrome, severe fever with thrombocytopenia syndrome virus, antiviral, ribavirin, favipiravir Frontiers in Microbiology | www.frontiersin.org

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“…Vaccine development for SFTS is at an early discovery phase and there have only been a few studies on vaccine candidates using animal infection models [8][9][10][11]. Immunization of NS antigen with Freund's adjuvant in C57BL/6 mice, which are naturally resistant to SFTSV but partially mimic human infections [12], failed to enhance viral clearance, although it induced high titer of anti-NS antibodies and significantly elevated IFN-γ levels in sera upon viral challenge [9].…”

Section: Introductionmentioning

confidence: 99%

Vaccination with single plasmid DNA encoding IL-12 and antigens of severe fever with thrombocytopenia syndrome virus elicits complete protection in IFNAR knockout mice

et al. 2020

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Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by SFTS virus (SFTSV) infection. Despite a gradual increase of SFTS cases and high mortality in endemic regions, no specific viral therapy nor vaccine is available. Here, we developed a single recombinant plasmid DNA encoding SFTSV genes, Gn and Gc together with NP-NS fusion antigen, as a vaccine candidate. The viral antigens were fused with Fmslike tyrosine kinase-3 ligand (Flt3L) and IL-12 gene was incorporated into the plasmid to enhance cell-mediated immunity. Vaccination with the DNA provides complete protection of IFNAR KO mice upon lethal SFTSV challenge, whereas immunization with a plasmid without IL-12 gene resulted in partial protection. Since we failed to detect antibodies against surface glycoproteins, Gn and Gc, in the immunized mice, antigen-specific cellular immunity, as confirmed by enhanced antigen-specific T cell responses, might play major role in protection. Finally, we evaluated the degree of protective immunity provided by protein immunization of the individual glycoprotein, Gn or Gc. Although both protein antigens induced a significant level of neutralizing activity against SFTSV, Gn vaccination resulted in relatively higher neutralizing activity and better protection than Gc vaccination. However, both antigens failed to provide complete protection. Given that DNA vaccines have failed to induce sufficient immunogenicity in human trials when compared to protein vaccines, optimal combinations of DNA and protein elements, proper selection of target antigens, and incorporation of efficient adjuvant, need to be further investigated for SFTSV vaccine development.

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Single dose of a rVSV-based vaccine elicits complete protection against severe fever with thrombocytopenia syndrome virus

Cited by 53 publications

References 50 publications

Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens

Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens

Antiviral Drugs Against Severe Fever With Thrombocytopenia Syndrome Virus Infection

Vaccination with single plasmid DNA encoding IL-12 and antigens of severe fever with thrombocytopenia syndrome virus elicits complete protection in IFNAR knockout mice

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