Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease

Wu, Xiaoxin; Yao, Hang‐Ping; Wu, Nanping; Gao, Hainv; Wu, Hai-bo; Jin, Changzhong; Lu, Xiangyun; Xie, Tian-Shen; Li, Lanjuan

doi:10.1159/000438531

Cited by 9 publications

(17 citation statements)

References 113 publications

(97 reference statements)

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“…The resurgence of the 2018 EVD epidemic in eastern DRC reminds us that there is still the threat of filovirus infection around the world. Subunit vaccines are a promising platform to prevent EBOV infection due to their relative safety, induction of effective immune responses, and available methods for high-level production [28]. GP is a promising candidate antigen for an EBOV protein vaccine.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Ebola virus exhibits a high degree of pathogenicity, transmissibility and could potentially be used as a bioterrorism agent [97]. Ebola viruses are classified as 'category A' pathogens causing lethal hemorrhagic fever.…”

Section: Ebola Virusmentioning

confidence: 99%

“…Traveling between countries for tourism, trading and medical assistance has resulted in increased global transmission, reminding us that Ebola virus disease is not limited to a particular region. Their possible misuse as bioterrorism agents may lead to a public safety catastrophe due to the lack of available therapeutics and vaccines [97][98][99].…”

Section: Ebola Virusmentioning

confidence: 99%

“…The first Ebola virus vaccine produced was an inactivated virus vaccine, which was tested for efficacy in guinea pigs in 1980 and showed protection, however, another study revealed opposing results [97,100]. In the following years, an increasing number of conventional Ebola virus vaccines were developed and tested through inactivation of the virus by using formalin, heat or gamma radiations [101].…”

Section: Ebola Virusmentioning

confidence: 99%

“…However, cutting-edge genetic engineering technologies have provided innovative approaches to designing better vaccine candidates. A number of modern vaccines against Ebola virus have been developed and are in preclinical or clinical trials, including DNA vaccines and Ebola virus like particles [97].…”

Section: Ebola Virusmentioning

confidence: 99%

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Cell Culture-based Viral Vaccines: Current Status and Future Prospects

et al. 2016

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Cell culture-based viral vaccines are used globally to immunize humans against infections. The cell culture is continuous process of developing substrates for the safe production of viral vaccines. However, increased global demand and strict safety rules for novel vaccines to control and eradicate viral diseases have forced researchers and manufacturers toward cell culture-based vaccines. The choice of cell substrate is a critical step that cannot be generalized for every vaccine formulation, therefore, manufacturers intend to optimize the required processes for particular applications. The recently established cell lines, innovative bioreactor concepts and cultivation schemes are necessary to increase the potential of vaccine production. In this review, we have focused on current cell culture-based viral vaccines and their future prospects. KEYWORDSThe use of vaccines to immunize humans and animals from infectious diseases has been documented for many years. Vaccination has been considered as the best operational approach to prevent infectious diseases, therefore, vaccine research and manufacturing is essential for the eradication and prevention of diseases throughout the world. Presently, more than 50 cell culture-based vaccines for human viral infectious agents are being manufactured, with many more at the research or developmental stages. Vaccination involves the administration of inactivated or attenuated infectious agents or subunit vaccines, which delivers the antigenic structures and provokes the adaptive immune system to ensure effective response against particular infections. Another method for the production of viral vaccines, egg-based production, is still the most widely used method to generate approximately 500 million vaccine doses and has been used for more than 60 years [1]. The increased vaccine demand and the potential threats of epidemics and pandemics have boosted the needs to introduce new manufacturing approaches for viral vaccines. The egg-based viral vaccine production is insufficient to fulfill the vaccine demands in cases of epidemics and pandemics due to unavailability of eggs. The egg-based vaccine production is only capable of an estimated yield of one vaccine dosage per one to two eggs. The current manufacturing capacity has to be projected for the production of almost 1420 million doses [1], therefore, it is essential to increase the existing vaccine production by a factor of 1.5 per year to immunize the global population against viral infections that cannot be achieved only by the egg-based system [2]. Therefore, many countries have initiated

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