The vesicular stomatitis virus-based Ebola virus vaccine: From concept to clinical trials

Suder, Ellen L.; Furuyama, Wakako; Feldmann, Heinz; Marzi, Andrea; Wit, Emmie de

doi:10.1080/21645515.2018.1473698

Cited by 111 publications

(84 citation statements)

References 54 publications

(59 reference statements)

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“…In this study, we used the well-characterized VSV-EBOV vaccine as our starting platform as it has advantages over other vaccine approaches such as ease of genetic modification, efficient and cost-effective manufacturing, proven human safety and immunogenicity profile, and potential favorable immune cell targeting. 27,28 To define a more optimized vaccine approach, we generated several different VSV-EBOV-based vaccine vectors and compared the protective efficacy against HPAI H5N1 virus challenge in the mouse model to a VSV-HAfl vector without the EBOV GP. Despite promising results from previous studies in chickens showing that adjuvanted subunit vaccines consisting of the trimeric H5 sHA (sHAzip) induced high levels of cross-neutralizing antibodies (clade 1 and 2.3.4), 34,35 we could not demonstrate convincing protection with the sHAzip-expressing VSV vectors in this study ( Fig.…”

Section: Discussionmentioning

confidence: 99%

“…32,36,40 This is an important observation, as lower-dose vaccination would likely reduce potential adverse effects of vaccination as has been reported ocassionally from human clinical trials using VSV-EBOV vaccination. 27 Recently, it has been shown that low-dose vaccination with VSV-EBOV does not compromise protective efficacy in nonhuman primates. 41 Lower-dose vaccination would also have a beneficial effect on vaccine manufacturing.…”

Section: Discussionmentioning

confidence: 99%

“…[22][23][24][25][26] Especially, the VSV-based Ebola virus (EBOV) vaccine, VSV-EBOV (also known as rVSV-ZEBOV or Ervebo), which expresses the EBOV GP instead of the VSV GP, is considered safe and highly immunogenic based on data from multiple clinical trials. 27,28 Noteworthy, VSV-EBOV has shown promising efficacy against EBOV in a phase III clinical trial 28 and is currently being used in the Democratic Republic of the Congo during the ongoing EBOV outbreak. 29 The promising safety profile of this liveattenuated vaccine and the favorable immune cell targeting mediated by the EBOV GP makes VSV-EBOV an interesting platform for vaccine development.…”

Section: Introductionmentioning

confidence: 99%

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A single dose of a vesicular stomatitis virus-based influenza vaccine confers rapid protection against H5 viruses from different clades

et al. 2020

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The avian influenza virus outbreak in 1997 highlighted the potential of the highly pathogenic H5N1 virus to cause severe disease in humans. Therefore, effective vaccines against H5N1 viruses are needed to counter the potential threat of a global pandemic. We have previously developed a fast-acting and efficacious vaccine against Ebola virus (EBOV) using the vesicular stomatitis virus (VSV) platform. In this study, we generated recombinant VSV-based H5N1 influenza virus vectors to demonstrate the feasibility of this platform for a fast-acting pan-H5 influenza virus vaccine. We chose multiple approaches regarding antigen design and genome location to define a more optimized vaccine approach. After the VSV-based H5N1 influenza virus constructs were recovered and characterized in vitro, mice were vaccinated by a single dose or prime/boost regimen followed by challenge with a lethal dose of the homologous H5 clade 1 virus. We found that a single dose of VSV vectors expressing full-length hemagglutinin (HAfl) were sufficient to provide 100% protection. The vaccine vectors were fast-acting as demonstrated by uniform protection when administered 3 days prior to lethal challenge. Moreover, single vaccination induced cross-protective H5-specific antibodies and protected mice against lethal challenge with various H5 clade 2 viruses, highlighting the potential of the VSV-based HAfl as a pan-H5 influenza virus emergency vaccine.npj Vaccines (2020) 5:4 ; https://doi.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A single dose of a vesicular stomatitis virus-based influenza vaccine confers rapid protection against H5 viruses from different clades

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“…To combine the efficacy of a LAV with the safety profile of an inactivated or subunit/DNA vaccine, well-characterized safe and efficacious vaccine strains can be genetically engineered to present critical antigens of the emerging pathogen of interest. A recent example is the Ebola vaccine, which showed efficacy in a phase III trial (25) and is based on vesicular stomatitis virus (VSV). Among others, measles virus (MV) vaccine strains have been developed as a platform technology for vaccine development (26) and have shown immunogenicity and efficacy against flavivirus infections in animal models for DENV (27), West Nile virus (28), and Japanese encephalitis virus (29).…”

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confidence: 99%

A Measles Virus-Based Vaccine Candidate Mediates Protection against Zika Virus in an Allogeneic Mouse Pregnancy Model

Nürnberger

Bodmer

Fiedler

et al. 2019

J Virol

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The impact of the Zika virus (ZIKV) epidemic highlights the need for vaccines that reduce or prevent infection and reliably prevent teratogenic complications. The live-attenuated measles virus (MV) vaccine strains are a promising vaccine platform, since they induce robust humoral and cellular immune responses against additional antigens and have an excellent safety record. To explore its potential to protect against ZIKV, we compared a recombinant Schwarz strain MV that encodes ZIKV prM and soluble E proteins (MV-Zika-sE) with a prototypic alum-adjuvanted whole inactivated ZIKV particle vaccine. Analysis of MV-Zika-sE-infected cells confirmed antigen expression, and the virus replicated with vaccine strain characteristics. Immunized IFNAR Ϫ/Ϫ -CD46Ge mice developed E protein-specific and neutralizing antibodies, and ZIKV E-specific cellular immune responses were observed by gamma interferon (IFN-␥) enzyme-linked immunospot (ELISpot) and in vitro T cell proliferation assays. To analyze protective efficacy, vaccinated female mice were challenged with ZIKV after allogeneic mating. In MV-Zika-sE-vaccinated mice, weight gain was similar to that in uninfected mice, while no plasma viremia was detectable in the majority of the animals. In contrast, infected control animals gained less weight and experienced about 100-fold higher viremia over at least 3 days. Moreover, vaccination with MV-Zika-sE reduced the ZIKV load in different organs and the placentas and prevented infection of the fetus. Consequently, no fetal growth retardation, anemia, or death due to ZIKV infection was seen in MV-Zika-sE-vaccinated dams. In contrast, the inactivated ZIKV vaccine had little to no effect in our studies. Therefore, the MV-derived ZIKV vaccine is a promising candidate for further preclinical and clinical development. IMPORTANCE Zika virus (ZIKV) is a mosquito-borne flavivirus that causes a variety of neurological complications, including congenital birth defects. Despite the urgent need, no ZIKV vaccine has yet been licensed. Recombinant vaccine strain-derived measles viruses (MV) constitute a promising vector platform to induce immunity against foreign pathogens by expressing antigens from additional transcription units while at the same time possessing a remarkable safety profile. This concept has already been validated against different pathogens, including at least 3 other flaviviruses, and our data show that vaccination with MV expressing soluble ZIKV E protein significantly diminishes infection and prevents fetal loss or damage in an allogeneic mouse pregnancy model. It can thus be regarded as a promising emergency vaccine candidate with the potential for inclusion in routine vaccination settings in areas of endemicity to prevent teratogenic effects of circulating ZIKV during pregnancy, comparable to standard rubella virus vaccination.

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“…Most notably, a number of the candidate vaccines currently under clinical phase evaluation are viral vector-based vaccines [15,16]. While recombinant vesicular stomatitis virus (rVSV)-based and recombinant adenovirus type-5 vector (rAd5)-based EBOV candidate vaccines have been shown to be highly efficacious against EBOV infection and transmission, numerous side effects, such as fever, acute arthritis, and skin lesions, have been reported [15,17,18]. In addition, preexisting antibodies, costs, and side effects should also be considered.…”

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confidence: 99%

A Novel Bacterium-Like Particle-Based Vaccine Displaying the SUDV Glycoprotein Induces Potent Humoral and Cellular Immune Responses in Mice

Jiao

Jin

et al. 2019

Viruses

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Sudan virus (SUDV) causes severe lethal hemorrhagic fever in humans and nonhuman primates. The most effective and economical way to protect against Sudan ebolavirus disease is prophylactic vaccination. However, there are no licensed vaccines to prevent SUDV infections. In this study, a bacterium-like particle (BLP)-based vaccine displaying the extracellular domain of the SUDV glycoprotein (eGP) was developed based on a gram-positive enhancer matrix-protein anchor (GEM-PA) surface display system. Expression of the recombinant GEM-displayed eGP (eGP-PA-GEM) was verified by Western blotting and immunofluorescence assays. The SUDV BLPs (SBLPs), which were mixed with Montanide ISA 201VG plus Poly (I:C) combined adjuvant, could induce high SUDV GP-specific IgG titers of up to 1:40,960 and robust virus-neutralizing antibody titers reached 1:460. The SBLP also elicited T-helper 1 (Th1) and T-helper 2 (Th2) cell-mediated immunity. These data indicate that the SBLP subunit vaccine has the potential to be developed into a promising candidate vaccine against SUDV infections. Viruses 2019, 11, 1149 2 of 15 and receiving unprecedented attention worldwide [4]. Unfortunately, an EVD outbreak occurred again in 2018 in eastern Democratic Republic of Congo and, as of August 2019, a total of 2997 EVD cases had been reported, including 2892 confirmed cases with 1998 deaths (overall case fatality rate of 67%) [5]. Since the first outbreak was reported in 1976, five different species of ebolaviruses, including Ebola virus (EBOV), Sudan virus (SUDV), Reston virus (RESTV), Bundibugyo virus (BDBV), and Taï Forest virus (TAFV,) have been identified and their genomic sequences differ by~35-45% [2]. Excluding EBOV, SUDV has the highest mortality and outbreak rates among the species of ebolaviruses. SUDV has emerged at least six times with average mortality rates of up to 53.76% [6,7]. Multiple vaccines and monoclonal antibodies against EBOV have been developed, but very few of them can effectively prevent and control SUDV infection [8]. Therefore, there is an urgent need to develop a safe and efficacious vaccine against SUDV.The EBOV genome encodes nine structural proteins, including the surface envelope glycoprotein (GP) as the only membrane protein [9]. The mature GP protein forms homotrimers on the surface of infected cells and virions, which is crucial for receptor binding, viral entry, and host immunity induction, making GP an ideal vaccine target [10]. A number of candidate vaccines for EBOV have demonstrated protection against lethal EBOV challenge in animal models and progressed to clinical trials, and most of these vaccines, including DNA vaccines [11], vaccines based on viral vectors, such as recombinant adenovirus [12] and vesicular stomatitis virus (VSV) [13], and protein-based vaccines, such as virus-like particles (VLPs) [14], have been based on GP. Most notably, a number of the candidate vaccines currently under clinical phase evaluation are viral vector-based vaccines [15,16]. While recombinant vesicular stomatitis virus (rVS...

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The vesicular stomatitis virus-based Ebola virus vaccine: From concept to clinical trials

Cited by 111 publications

References 54 publications

A single dose of a vesicular stomatitis virus-based influenza vaccine confers rapid protection against H5 viruses from different clades

A single dose of a vesicular stomatitis virus-based influenza vaccine confers rapid protection against H5 viruses from different clades

A Measles Virus-Based Vaccine Candidate Mediates Protection against Zika Virus in an Allogeneic Mouse Pregnancy Model

A Novel Bacterium-Like Particle-Based Vaccine Displaying the SUDV Glycoprotein Induces Potent Humoral and Cellular Immune Responses in Mice

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