Ebola virus: the search for vaccines and treatments

Wilson, Julie A.; Bosio, Catharine M.; Hart, Mary Kate

doi:10.1007/pl00000821

Cited by 40 publications

(33 citation statements)

References 98 publications

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“…eVLPs lack the viral genome and have no replicative ability and thus deliver the predominant structural antigens without the possibility of infection with EBOV or a carrier vector (6,12,16). Additionally, eVLPs are composed of only EBOV GP and VP40 and lack other viral proteins, such as VP35, that are potentially immunosuppressive (51).…”

Section: Discussionmentioning

confidence: 99%

“…Some of these vaccine strategies are efficacious in nonhuman primates against MARV but not EBOV (8,10). In contrast with previous disappointments involving several vaccine approaches in nonhuman primates (6,14,15), sequential administration of a DNA vaccine and Ͼ10 10 plaque-forming units (pfu) of a defective adenovirus-vectored vaccine or the adenovirus vaccine alone protected nonhuman primates against an EBOV challenge (16)(17)(18). Although offering an important proof of concept to be pursued, much remains uncertain about the latter strategy, including an acceptable vaccine dose and the impact of prior immunity to the adenovirus used (19).…”

mentioning

confidence: 94%

“…A vaccine against filoviruses is needed that protects against a natural or nosocomial outbreak, laboratory accident, or malevolent airborne attack. As of now, there are no available vaccines and no immunological or pharmacological therapies, in part, because of limited knowledge of the mechanisms of filovirus pathogenesis and immunity (6).…”

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confidence: 99%

“…Although offering an important proof of concept to be pursued, much remains uncertain about the latter strategy, including an acceptable vaccine dose and the impact of prior immunity to the adenovirus used (19). Thus, there is still a need to explore vaccines against EBOV that do not face these challenges or the particular challenges of other vectored, live-attenuated, or killed virus vaccine strategies (6,14,15).…”

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confidence: 99%

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Ebola virus-like particles protect from lethal Ebola virus infection

Warfield

Bosio

Welcher

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

228

258

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The filovirus Ebola causes hemorrhagic fever with 70 -80% human mortality. High case-fatality rates, as well as known aerosol infectivity, make Ebola virus a potential global health threat and possible biological warfare agent. Development of an effective vaccine for use in natural outbreaks, response to biological attack, and protection of laboratory workers is a higher national priority than ever before. Coexpression of the Ebola virus glycoprotein (GP) and matrix protein (

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 94%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Ebola virus-like particles protect from lethal Ebola virus infection

Warfield

Bosio

Welcher

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

228

258

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“…A number of experimental vaccination strategies are being explored, including soluble viral proteins, DNA vaccines, replicons and a combination of DNA and replication-deficient adenovirus preparations. Given the importance of both the cellular and humoral immune response for protection against filoviruses, VLPs represent an excellent vaccine candidate [60,64,70,96] Besides their use as vaccines, VLPs are being used to better understand the immune responses to filoviruses, with the aim of developing immunotherapeutics for treating EBOV and MARV infections. In addition, the EBOV and MARV VLPs are being used to investigate the life cycle of these viruses with the ultimate goal of developing rationally designed therapeutics.…”

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confidence: 99%

Filovirus-like particles as vaccines and discovery tools

Warfield

Swenson

Demmin

et al. 2005

Expert Review of Vaccines

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Ebola and Marburg viruses are members of the family Filoviridae, which cause severe hemorrhagic fevers in humans. Filovirus outbreaks have been sporadic, with mortality rates currently ranging from 30 to 90%. Unfortunately, there is no efficacious human therapy or vaccine available to treat disease caused by either Ebola or Marburg virus infection. Expression of the filovirus matrix protein, VP40, is sufficient to drive spontaneous production and release of virus-like particles (VLPs) that resemble the distinctively filamentous infectious virions. The addition of other filovirus proteins, including virion proteins (VP)24, 30 and 35 and glycoprotein, increases the efficiency of VLP production and results in particles containing multiple filovirus antigens. Vaccination with Ebola or Marburg VLPs containing glycoprotein and VP40 completely protects rodents from lethal challenge with the homologous virus. These candidate vaccines are currently being tested for immunogenicity and efficacy in nonhuman primates. Furthermore, the Ebola and Marburg VLPs are being used as a surrogate model to further understand the filovirus life cycle, with the goal of developing rationally designed vaccines and therapeutics. Thus, in addition to their use as a vaccine, VLPs are currently being used as tools to learn lessons about filovirus pathogenesis, immunology, replication and assembly requirements.Expert Rev. Vaccines 4(3), 429-440 (2005) Ebola (EBOV) and Marburg (MARV) viruses are the only members of the family Filoviridae, and were named according to their filamentous shape. EBOV and MARV cause acute and rapidly progressive hemorrhagic fever with mortality rates in humans of up to 90% [1,2]. The reservoir for filoviruses is unknown, although the consumption of monkey meat is often associated with onset of disease. Animals ranging from insects to mammals have been analyzed in the hopes of identifying a carrier, but to no avail [3]. After exposure, the onset of clinical symptoms can be as short as 2 days and as long as 21, although most infected humans and nonhuman primates die within 7-10 days of exposure [4]. In addition to hemorrhage and bleeding, other symptoms of filovirus infection include fever, headache, generalized myalgia, prostration, conjunctivitis, rash, lymphadenopathy, pharyngitis and edema [5].Filoviruses are considered serious public health threats, and are classified as biosafety level (BSL)-4 agents and Category A biothreat agents by the US Centers for Disease Control and Prevention [6,101]. Features that characterize filoviruses as a significant global health risk include high morbidity and mortality rates, potential for person-to-person transmission, relative stability in the environment, and feasibility of large-scale production. Additionally, the filoviruses have a low infectious dose, an extremely rapid rate of replication and can be easily transmitted, including via aerosols [4,7,8]. Bolstering the fear of their use as bioterrorism agents, several hemorrhagic fever viruses have a history of state-sponsor...

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Detection of Antibodies against the Four Subtypes of Ebola Virus in Sera from Any Species Using a Novel Antibody-Phage Indicator Assay

et al. 2002

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The natural host for Ebola virus, presumed to be an animal, has not yet been identified despite an extensive search following several major outbreaks in Africa. A straightforward approach used to determine animal contact with Ebola virus is by assessing the presence of specific antibodies in serum. This approach however has been made very difficult by the absence of specific reagents required for the detection of antibodies from the majority of wild animal species. In this study, we isolated a human monoclonal antibody Fab fragment, KZ51, that reacts with an immunodominant epitope on Ebola virus nucleoprotein (NP) that is conserved on all four Ebola virus subtypes. The antibody KZ51 represents a major specificity as sera from all convalescent patients tested (10/10) and sera from guinea pigs infected with each of the four Ebola virus subtypes competed strongly with KZ51 for binding to radiation-inactivated Ebola virus. These features allowed us to develop a novel assay for the detection of seroconversion irrespective of Ebola virus subtype or animal species. In this assay, the binding of KZ51 Fab-phage particles is used as an indicator assay and the presence of specific antibodies against Ebola virus in sera is indicated by binding competition. A prominent feature of the assay is that the Fab-phage particles may be prestained with a dye so that detection of binding can be directly determined by visual inspection. The assay is designed to be both simple and economical to enable its use in the field.

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Ebola virus: the search for vaccines and treatments

Cited by 40 publications

References 98 publications

Ebola virus-like particles protect from lethal Ebola virus infection

Ebola virus-like particles protect from lethal Ebola virus infection

Filovirus-like particles as vaccines and discovery tools

Detection of Antibodies against the Four Subtypes of Ebola Virus in Sera from Any Species Using a Novel Antibody-Phage Indicator Assay

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