Ebola virus disease candidate vaccines under evaluation in clinical trials

Martins, Karen; Jahrling, Peter B.; Bavari, Sina; Kuhn, Jens H.

doi:10.1080/14760584.2016.1187566

Cited by 51 publications

(42 citation statements)

References 106 publications

(98 reference statements)

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“…Both MARV and EBOV have caused numerous outbreaks throughout Africa, and EBOV is responsible for the 2013–2015 West African epidemic that infected over 28,000 people and left over 11,000 dead (World Health Organization, 2016). No vaccine is currently approved to prevent filovirus disease, although many candidates have shown efficacy in non-human primates as well as in human trials conducted during the West African Ebola epidemic (Feldmann et al, 2013; Martins et al, 2016). Likewise, no drug candidate has been approved for use, but several candidates have been developed, including siRNAs, monoclonal antibodies, interferon, and estrogen receptor modulators (Johansen et al, 2013; Bixler et al, 2017; Connor et al, 2017; Olinger Jr et al, 2012; Qiu et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Successful treatment of Marburg virus with orally administrated T-705 (Favipiravir) in a mouse model

Zhu

Zhang

et al. 2018

Antiviral Research

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Filoviruses, such as Marburg and Ebola viruses, cause severe disease in humans with high case fatality rates and are therefore considered biological threat agents. To date, no licensed vaccine or therapeutic exists for their treatment. T-705 (favipiravir) is a pyrazinecarboxamide derivative that has shown broad antiviral activity against a number of viruses and is clinically licenced in Japan to treat influenza. Here we report the efficacy of T-705 against Marburg virus infection in vitro and in vivo. Notably, oral administration of T-705 beginning one or two days post-infection and continuing for eight days resulted in complete survival of mice that had been intraperitoneally infected with mouse-adapted Marburg virus (variant Angola). Moreover, lower doses of T-705 and higher doses administered later during infection (day 3 or 4 post-infection) showed partial efficacy, with at least half the infected mice surviving. Accordingly, we observed reductions in infectious virus particles and virus RNA levels following drug treatment that appeared to correlate with survival. Our findings suggest that T-705 may be an effective therapeutic against Marburg virus and might be especially promising for use in the event of an outbreak, where it could be orally administered quickly and safely even after exposure.

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Section: Introductionmentioning

confidence: 99%

Successful treatment of Marburg virus with orally administrated T-705 (Favipiravir) in a mouse model

Zhu

Zhang

et al. 2018

Antiviral Research

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“…The success of the VSV vectored Ebola Zaire vaccine in human trials implies that vaccines can be made against the other related filoviruses, and there is general agreement that protection should be ensured against at least Ebola Sudan, Bundibugyo, and Marburg viruses. [17][18][19] However, unless fortuitous outbreaks occur we will be unable to demonstrate the efficacy of those other filovirus vaccines except by determination of correlates of protection in 2 relevant animal models or by analogy to human responses to Ebola Zaire vaccine. It is not yet clear how CEPI will choose among the many filovirus candidate vaccines.…”

Section: The Short Term: Filoviruses and Chikungunyamentioning

confidence: 99%

Vaccines for epidemic infections and the role of CEPI

Plotkin

2017

Human Vaccines & Immunotherapeutics

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“…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 (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].…”

mentioning

confidence: 99%

“…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.…”

mentioning

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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Ebola virus disease candidate vaccines under evaluation in clinical trials

Cited by 51 publications

References 106 publications

Successful treatment of Marburg virus with orally administrated T-705 (Favipiravir) in a mouse model

Successful treatment of Marburg virus with orally administrated T-705 (Favipiravir) in a mouse model

Vaccines for epidemic infections and the role of CEPI

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

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