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Immunization of knock-out α/β interferon receptor mice against high lethal dose of Crimean-Congo hemorrhagic fever virus with a cell culture based vaccine.

Canakoglu N, Berber E, Tonbak S, Ertek M, Sozdutmaz I, Aktas M, Kalkan A, Ozdarendeli A - PLoS Negl Trop Dis (2015)

Bottom Line: The disease has been reported in many countries of Africa, Asia, the Middle East, and in Eurasia.During the past decade, new foci of CCHF have emerged in the Balkan Peninsula, southwest Russia, the Middle East, western China, India, Africa, and Turkey.Vaccine development efforts have been significantly hampered by a lack of animal models and therefore, no protective vaccine has been achieved.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Medical Faculty, Erciyes University, Kayseri, Turkey; Department of Virology, College of Veterinary Medicine, Firat University, Elazig, Turkey.

ABSTRACT
Crimean-Congo hemorrhagic fever (CCHF) is an acute tick-borne zoonotic disease. The disease has been reported in many countries of Africa, Asia, the Middle East, and in Eurasia. During the past decade, new foci of CCHF have emerged in the Balkan Peninsula, southwest Russia, the Middle East, western China, India, Africa, and Turkey. CCHF virus produces severe hemorrhagic manifestations in humans with fatality rates up to 30%. Vaccine development efforts have been significantly hampered by a lack of animal models and therefore, no protective vaccine has been achieved. Lately, IFN α/β receptor deficient (IFNAR-/-) mice have been established as a novel small animal model of CCHF virus infection. In the present study, we found that IFNAR-/- mice highly susceptible to CCHF virus Turkey-Kelkit06 strain. Immunization with the cell culture based vaccine elicited a significant level of protection against high dose challenge (1,000 PPFU) with a homologous CCHF virus in IFNAR-/- mice.

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Related in: MedlinePlus

Protection of IFNAR−/− mice immunized with the cell culture based vaccine against CCHF virus Turkey-Kelkit06 strain challenge.Groups of 6 IFNAR−/− mice were immunized three times at three weeks intervals with 5, 20, or 40 μg of the cell culture based vaccine. The control group of IFNAR−/− mice (n = 6) was mock immunized with phosphate buffered solution (PBS). All animals were challenged with 1,000 PPFU (400 LD50) of CCHF virus Turkey- Kelkit06 strain two weeks after the last immunization. The mice were monitored twice daily for the cumulative mean symptom scores (A), the daily variations in weight as percentages compared to before the virus challenge (B), body temperature (C), and geometric mean time to death and survival (D). The animals were monitored for three weeks after the challenge. The standard deviations are shown as error bars.
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pntd.0003579.g004: Protection of IFNAR−/− mice immunized with the cell culture based vaccine against CCHF virus Turkey-Kelkit06 strain challenge.Groups of 6 IFNAR−/− mice were immunized three times at three weeks intervals with 5, 20, or 40 μg of the cell culture based vaccine. The control group of IFNAR−/− mice (n = 6) was mock immunized with phosphate buffered solution (PBS). All animals were challenged with 1,000 PPFU (400 LD50) of CCHF virus Turkey- Kelkit06 strain two weeks after the last immunization. The mice were monitored twice daily for the cumulative mean symptom scores (A), the daily variations in weight as percentages compared to before the virus challenge (B), body temperature (C), and geometric mean time to death and survival (D). The animals were monitored for three weeks after the challenge. The standard deviations are shown as error bars.

Mentions: Following the three inoculations with the cell culture based vaccine containing 5, 20, and 40 μg, the IFNAR−/− mice were challenged with 1,000 PPFU (400 LD50) of CCHF virus Turkey-Kelkit06 strain two weeks after the last immunization. Survival was assessed over a period of three weeks. The control group of 6 IFNAR−/− mice showed signs of the disease, manifested as rapid weight loss at 2 days post-challenge (Fig. 4A and 4B). All became hypothermic and were euthanized at 3 days post challenge (Fig. 4C and 4D).


Immunization of knock-out α/β interferon receptor mice against high lethal dose of Crimean-Congo hemorrhagic fever virus with a cell culture based vaccine.

Canakoglu N, Berber E, Tonbak S, Ertek M, Sozdutmaz I, Aktas M, Kalkan A, Ozdarendeli A - PLoS Negl Trop Dis (2015)

Protection of IFNAR−/− mice immunized with the cell culture based vaccine against CCHF virus Turkey-Kelkit06 strain challenge.Groups of 6 IFNAR−/− mice were immunized three times at three weeks intervals with 5, 20, or 40 μg of the cell culture based vaccine. The control group of IFNAR−/− mice (n = 6) was mock immunized with phosphate buffered solution (PBS). All animals were challenged with 1,000 PPFU (400 LD50) of CCHF virus Turkey- Kelkit06 strain two weeks after the last immunization. The mice were monitored twice daily for the cumulative mean symptom scores (A), the daily variations in weight as percentages compared to before the virus challenge (B), body temperature (C), and geometric mean time to death and survival (D). The animals were monitored for three weeks after the challenge. The standard deviations are shown as error bars.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356576&req=5

pntd.0003579.g004: Protection of IFNAR−/− mice immunized with the cell culture based vaccine against CCHF virus Turkey-Kelkit06 strain challenge.Groups of 6 IFNAR−/− mice were immunized three times at three weeks intervals with 5, 20, or 40 μg of the cell culture based vaccine. The control group of IFNAR−/− mice (n = 6) was mock immunized with phosphate buffered solution (PBS). All animals were challenged with 1,000 PPFU (400 LD50) of CCHF virus Turkey- Kelkit06 strain two weeks after the last immunization. The mice were monitored twice daily for the cumulative mean symptom scores (A), the daily variations in weight as percentages compared to before the virus challenge (B), body temperature (C), and geometric mean time to death and survival (D). The animals were monitored for three weeks after the challenge. The standard deviations are shown as error bars.
Mentions: Following the three inoculations with the cell culture based vaccine containing 5, 20, and 40 μg, the IFNAR−/− mice were challenged with 1,000 PPFU (400 LD50) of CCHF virus Turkey-Kelkit06 strain two weeks after the last immunization. Survival was assessed over a period of three weeks. The control group of 6 IFNAR−/− mice showed signs of the disease, manifested as rapid weight loss at 2 days post-challenge (Fig. 4A and 4B). All became hypothermic and were euthanized at 3 days post challenge (Fig. 4C and 4D).

Bottom Line: The disease has been reported in many countries of Africa, Asia, the Middle East, and in Eurasia.During the past decade, new foci of CCHF have emerged in the Balkan Peninsula, southwest Russia, the Middle East, western China, India, Africa, and Turkey.Vaccine development efforts have been significantly hampered by a lack of animal models and therefore, no protective vaccine has been achieved.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Medical Faculty, Erciyes University, Kayseri, Turkey; Department of Virology, College of Veterinary Medicine, Firat University, Elazig, Turkey.

ABSTRACT
Crimean-Congo hemorrhagic fever (CCHF) is an acute tick-borne zoonotic disease. The disease has been reported in many countries of Africa, Asia, the Middle East, and in Eurasia. During the past decade, new foci of CCHF have emerged in the Balkan Peninsula, southwest Russia, the Middle East, western China, India, Africa, and Turkey. CCHF virus produces severe hemorrhagic manifestations in humans with fatality rates up to 30%. Vaccine development efforts have been significantly hampered by a lack of animal models and therefore, no protective vaccine has been achieved. Lately, IFN α/β receptor deficient (IFNAR-/-) mice have been established as a novel small animal model of CCHF virus infection. In the present study, we found that IFNAR-/- mice highly susceptible to CCHF virus Turkey-Kelkit06 strain. Immunization with the cell culture based vaccine elicited a significant level of protection against high dose challenge (1,000 PPFU) with a homologous CCHF virus in IFNAR-/- mice.

Show MeSH
Related in: MedlinePlus