Fighting Ebola: A Window for Vaccine Re-evaluation?

Chappell, Keith J.; Watterson, Daniel

doi:10.1371/journal.ppat.1006037

Cited by 14 publications

(15 citation statements)

References 34 publications

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“…While the efficacies of several EBOV candidate vaccines and therapeutic strategies are currently being assessed, supportive care remains the primary method of treatment ( 2 ). Moreover, despite a moderate efficiency, EBOV candidate vaccines are associated with harmful side effects, including high levels of inflammation and lymphopenia ( 3 – 6 ). Unraveling the complex and multiple mechanisms employed by EBOV that lead to rapid disease progression remains critical to the development of postexposure therapeutic interventions.…”

Section: Introductionmentioning

confidence: 99%

Ebola Virus Binding to Tim-1 on T Lymphocytes Induces a Cytokine Storm

Younan

Iampietro

Nishida

et al. 2017

mBio

101

114

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Ebola virus (EBOV) disease (EVD) results from an exacerbated immunological response that is highlighted by a burst in the production of inflammatory mediators known as a “cytokine storm.” Previous reports have suggested that nonspecific activation of T lymphocytes may play a central role in this phenomenon. T-cell immunoglobulin and mucin domain-containing protein 1 (Tim-1) has recently been shown to interact with virion-associated phosphatidylserine to promote infection. Here, we demonstrate the central role of Tim-1 in EBOV pathogenesis, as Tim-1−/− mice exhibited increased survival rates and reduced disease severity; surprisingly, only a limited decrease in viremia was detected. Tim-1−/− mice exhibited a modified inflammatory response as evidenced by changes in serum cytokines and activation of T helper subsets. A series of in vitro assays based on the Tim-1 expression profile on T cells demonstrated that despite the apparent absence of detectable viral replication in T lymphocytes, EBOV directly binds to isolated T lymphocytes in a phosphatidylserine–Tim-1-dependent manner. Exposure to EBOV resulted in the rapid development of a CD4Hi CD3Low population, non-antigen-specific activation, and cytokine production. Transcriptome and Western blot analysis of EBOV-stimulated CD4+ T cells confirmed the induction of the Tim-1 signaling pathway. Furthermore, comparative analysis of transcriptome data and cytokine/chemokine analysis of supernatants highlight the similarities associated with EBOV-stimulated T cells and the onset of a cytokine storm. Flow cytometry revealed virtually exclusive binding and activation of central memory CD4+ T cells. These findings provide evidence for the role of Tim-1 in the induction of a cytokine storm phenomenon and the pathogenesis of EVD.

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Section: Introductionmentioning

confidence: 99%

Ebola Virus Binding to Tim-1 on T Lymphocytes Induces a Cytokine Storm

Younan

Iampietro

Nishida

et al. 2017

mBio

101

114

View full text Add to dashboard Cite

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“…The delayed recognition of the Ebola outbreak led to overwhelmed health care systems unable to contain the spread of the virus. Halted vaccine development and testing activities were resumed but relatively late during the course of the epidemic, and eventually the epidemic was contained by strict implementation of hygienic and sanitary measures [23]. However, several Ebola vaccine candidates and prime-boost regimens were tested pre-clinically and eventually also clinically in the affected area.…”

Section: Main Textmentioning

confidence: 99%

“…However, several Ebola vaccine candidates and prime-boost regimens were tested pre-clinically and eventually also clinically in the affected area. The trials were initiated mostly during the tail of the epidemic, but led to at least one effective vaccine [23]. This vaccine may be used in the face of a next Ebola outbreak, to protect healthcare workers and contacts of infected individuals, to control nosocomial and subsequent further spread in the population.…”

Section: Main Textmentioning

confidence: 99%

AIDS, Avian flu, SARS, MERS, Ebola, Zika… what next?

Reperant

Osterhaus

2017

Vaccine

140

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Emerging infections have threatened humanity since times immemorial. The dramatic anthropogenic, behavioral and social changes that have affected humanity and the environment in the past century have accelerated the intrusion of novel pathogens into the global human population, sometimes with devastating consequences. The AIDS and influenza pandemics have claimed and will continue to claim millions of lives. The recent SARS and Ebola epidemics have threatened populations across borders. The emergence of MERS may well be warning signals of a nascent pandemic threat, while the potential for geographical spread of vector-borne diseases, such as Zika, but also Dengue and Chikungunya is unprecedented. Novel technologies and innovative approaches have multiplied to address and improve response preparedness towards the increasing yet unpredictable threat posed by emerging pathogens.

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“…The other two advanced vaccines both utilize an adenovirus (AdV) vector. In these vaccines, the EBOV GP occupies the native adenovirus early region, furnishing a nonreplicating virus [18].…”

Section: Vaccinesmentioning

confidence: 99%

Advances in Tackling Filoviruses

Selaković

Šolaja

2018

Contributions

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Filoviruses are virulent pathogens that cause deadly haemorrhagic fever in humans and non-human primates. There is currently no approved drug or vaccine to tackle this disease. Two vaccine platforms that use adenovirus vectors have completed phase I studies, while a recombinant vesicular stomatitis virus-based vaccine has successfully complet-ed a phase III trial. Intricate macromolecular therapeutics have also been developed, most notably those based on anti-bodies or interfering RNA or RNA-surrogates. Most small molecules active against filoviruses have not yet advanced to clinical trials, except favipiravir, which was proven to be safe, and GS-5734, which has entered trials.

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Fighting Ebola: A Window for Vaccine Re-evaluation?

Cited by 14 publications

References 34 publications

Ebola Virus Binding to Tim-1 on T Lymphocytes Induces a Cytokine Storm

Ebola Virus Binding to Tim-1 on T Lymphocytes Induces a Cytokine Storm

AIDS, Avian flu, SARS, MERS, Ebola, Zika… what next?

Advances in Tackling Filoviruses

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