A Crimean-Congo hemorrhagic fever (CCHF) viral vaccine expressing nucleoprotein is immunogenic but fails to confer protection against lethal disease

Dowall, Stuart; Buttigieg, Karen; Findlay‐Wilson, Stephen; Rayner, Emma; Pearson, Geoffrey; Miloszewska, A; Graham, Victoria; Carroll, Miles W.; Hewson, Roger

doi:10.1080/21645515.2015.1078045

Cited by 88 publications

(87 citation statements)

References 67 publications

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“…Interestingly candidates have included a MVA construct expressing the CCHFV nucleoprotein, which generated antigen-specific immunity but showed no protection against a lethal virus challenge in A129 mice [99].…”

Section: Vaccine Progressmentioning

confidence: 99%

Development of vaccines against Crimean-Congo haemorrhagic fever virus

Dowall

Carroll

Hewson

2017

Vaccine

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Crimean-Congo haemorrhagic fever virus (CCHFV) is a deadly human pathogen of the utmost seriousness being highly lethal causing devastating disease symptoms that result in intense and prolonged suffering to those infected. During the past 40 years, this virus has repeatedly caused sporadic outbreaks responsible for relatively low numbers of human casualties, but with an alarming fatality rate of up to 80% in clinically infected patients. CCHFV is transmitted to humans by Hyalomma ticks and contact with the blood of viremic livestock, additionally cases of human-to-human transmission are not uncommon in nosocomial settings. The incidence of CCHF closely matches the geographical range of permissive ticks, which are widespread throughout Africa, Asia, the Middle East and Europe. As such, CCHFV is the most widespread tick-borne virus on earth. It is a concern that recent data shows the geographic distribution of Hyalomma ticks is expanding. Migratory birds are also disseminating Hyalomma ticks into more northerly parts of Europe thus potentially exposing naïve human populations to CCHFV. The virus has been imported into the UK on two occasions in the last five years with the first fatal case being confirmed in 2012. A licensed vaccine to CCHF is not available. In this review, we discuss the background and complications surrounding this limitation and examine the current status and recent advances in the development of vaccines against CCHFV.

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Section: Vaccine Progressmentioning

confidence: 99%

Development of vaccines against Crimean-Congo haemorrhagic fever virus

Dowall

Carroll

Hewson

2017

Vaccine

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“…Although acaricide treatment of animals, e.g., before or during marketing, is thought the be an effective intervention strategy and is linked to decreased seroprevalence (84,85), efficacy has not been sufficiently investigated. Ultimately, for these and other putative intervention strategies (e.g., anti-tick vaccines (86–88) or anti-CCHFV vaccines [90,91]), proper development, evaluation, and implementation would require a more detailed understanding of tick-host interactions and viral transmission.…”

Section: What We Still Do Not Knowmentioning

confidence: 99%

A chronological review of experimental infection studies of the role of wild animals and livestock in the maintenance and transmission of Crimean-Congo hemorrhagic fever virus

Spengler¹,

et al. 2016

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This article provides a definitive review of experimental studies of the role of wild animals and livestock in the maintenance and transmission of Crimean-Congo hemorrhagic fever virus (CCHFV), the etiologic agent of Crimean-Congo hemorrhagic fever (CCHF), beginning with the first recognized outbreak of the human disease in Crimea in 1944. Published reports by researchers in the former Soviet Union, Bulgaria, South Africa, and other countries where CCHF has been observed show that CCHFV is maintained in nature in a tick-vertebrate-tick enzootic cycle. Human disease most commonly results from the bite of an infected tick, but may also follow crushing of infected ticks or exposure to the blood and tissues of infected animals during slaughter. Wild and domestic animals are susceptible to infection with CCHFV, but do not develop clinical illness. Vertebrates are important in CCHF epidemiology, as they provide blood meals to support tick populations, transport ticks across wide geographic areas, and transmit CCHFV to ticks and humans during the period of viremia. Many aspects of vertebrate involvement in the maintenance and spread of CCHFV are still poorly understood. Experimental investigations in wild animals and livestock provide important data to aid our understanding of CCHFV ecology. This article is the second in a series of reviews of more than 70 years of research on CCHF, summarizing important findings, identifying gaps in knowledge, and suggesting directions for future research.

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“…This aggravates the research of specific anti-viral therapies as well as deeper knowledge about the host-virus interactions on a molecular level [178,179]. The Hazara virus is closely related to CCHFV.…”

Section: Virusmentioning

confidence: 99%

Aquaporins in Infection and Inflammation

Holm¹

2016

Linköping University Medical Dissertations

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About the cover:The front cover displays a human, blood-derived macrophage stained for aquaporin 9.During the course of the research underlying this thesis, Angelika Holm was enrolled in Forum Scientium, a multidisciplinary doctoral programme at Linköping University Printed by LiU-Tryck, Linköping, Sweden, 2016 "Be brave, even if you're not, pretend to be. No one can tell the difference."To that young, awkward, tall girl who dared to dream of something else, something more:You did it. SUPERVISOR Elena VikströmDepartment of Clinical and Experimental Medicine Linköping University Linköping Sweden When cells of the innate immune system encounter pathogens they need to respond and prepare for migration and phagocytosis and do so through volume regulatory processes. The Gramnegative bacterium Pseudomonas aeruginosa utilizes a small molecule-based communication system, called quorum sensing (QS) to control the production of its virulence factors and biofilms. We found that P. aeruginosa with a complete QS system elicits a stronger phagocytic response in human blood-derived macrophages compared to its lasI-/rhlI-mutant lacking the production of the QS molecules N-butyryl-L-homoserine lactone (C4-HSL) and N-3-oxododecanoyl-L-homoserine lactone (3O-C12-HSL). Infection with P. aeruginosa further increases the expression of AQP9 and induces re-localisation of AQP9 to the front and trailing ends of macrophages. Moreover, the 3O-C12-HSL alone elevates the expression of AQP9, redistribute the water channel to the front and rear ends and increases the cell area and volume of macrophages. Both infection with the wild type P. aeruginosa and the treatment with 3O-C12-HSL change the nano-structural architecture of the AQP9 distribution in macrophages. ASSISTANT SUPERVISORS Karl-Eric MagnussonViruses use the intracellular machinery of the invaded cells to produce and assemble new viral bodies. Intracellular AQPs are localised in a membranes of cellular organelles to regulate their function and morphology. C3H10T1/2 fibroblasts transiently expressing green fluorescent protein (GFP)-AQP6 show a reduced expression of AQP6 after Hazara virus infection and an increased cell area. Overexpressing AQP6 in C3H10T1/2 cells reduces the infectivity of Hazara virus indicating that AQP6 expression has a protective role in virus infections.Ion and water channels in the epithelial cell lining tightly regulate the water homeostasis. In microscopic colitis (MC), patients suffer from severe watery diarrhoeas. For the first time, we have shown that the expression of AQP1, 8 and 11 and the sodium/hydrogen exchanger NHE1 are reduced in colonic biopsies from MC patients compared to healthy control individuals. Following treatment with the glucocorticoid budesonide the patients experienced a rapid recovery and we observed a restored or increased expression of the AQPs and NHE1 during treatment, suggesting a role for AQPs in the diarrhoeal mechanisms in MC.Taken together, this thesis provides new evidence on the importance of water homeostasis regulatio...

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A Crimean-Congo hemorrhagic fever (CCHF) viral vaccine expressing nucleoprotein is immunogenic but fails to confer protection against lethal disease

Cited by 88 publications

References 67 publications

Development of vaccines against Crimean-Congo haemorrhagic fever virus

Development of vaccines against Crimean-Congo haemorrhagic fever virus

A chronological review of experimental infection studies of the role of wild animals and livestock in the maintenance and transmission of Crimean-Congo hemorrhagic fever virus

Aquaporins in Infection and Inflammation

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