Yellow fever virus isolated from a fatal post vaccination event: an experimental comparative study with the 17DD vaccine strain in the Syrian hamster (Mesocricetus auratus)

In order to investigate the pathogenicity of the virus strain GOI 4191 that was isolated from a fatal adverse event after yellow fever virus (YFV) vaccination, an experimental assay using hamsters (Mesocricetus auratus) as animal model and YFV 17DD vaccine strain as virus reference was accomplished. The two virus strains were inoculated by intracerebral, intrahepatic and subcutaneous routes. The levels of viremia, antibody response, and aminotransferases were determined in sera; while virus, antigen and histopathological changes were determined in the viscera. No viremia was detected for either strain following infection; the immune response was demonstrated to be more effective to strain GOI 4191; and no significant aminotransferase levels alterations were detected. Strain GOI 4191 was recovered only from the brain of animals inoculated by the IC route. Viral antigens were detected in liver and brain by immunohistochemical assay. Histothological changes in the viscera were characterized by inflammatory infiltrate, hepatocellular necrosis, and viral encephalitis. Histological alterations and detection of viral antigen were observed in the liver of animals inoculated by the intrahepatic route. These findings were similar for both strains used in the experiment; however, significant differences were observed from those results previously reported for wild type YFV strains.

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Differential cytokine responses from primary human Kupffer cells following infection with wild-type or vaccine strain yellow fever virus

Virology ◽

10.1016/j.virol.2011.01.012 ◽

2011 ◽

Vol 412 (1) ◽

pp. 188-195 ◽

Cited By ~ 17

Author(s):

Sara E. Woodson ◽

Alexander N. Freiberg ◽

Michael R. Holbrook

Keyword(s):

Yellow Fever ◽

Vaccine Strain ◽

Kupffer Cells ◽

Yellow Fever Virus ◽

Fever Virus ◽

Wild Type ◽

Cytokine Responses

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Development of a Real-Time Reverse Transcription-PCR Assay for Global Differentiation of Yellow Fever Virus Vaccine-Related Adverse Events from Natural Infections

Journal of Clinical Microbiology ◽

10.1128/jcm.00323-18 ◽

2018 ◽

Vol 56 (6) ◽

Cited By ~ 3

Author(s):

Holly R. Hughes ◽

Brandy J. Russell ◽

Eric C. Mossel ◽

John Kayiwa ◽

Julius Lutwama ◽

...

Keyword(s):

Adverse Events ◽

Real Time ◽

Yellow Fever ◽

Vaccine Strain ◽

Reverse Transcription ◽

Yellow Fever Virus ◽

Fever Virus ◽

Wild Type ◽

Pcr Assay ◽

Reverse Transcription Pcr

ABSTRACT Yellow fever (YF) is a reemerging public health threat, with frequent outbreaks prompting large vaccination campaigns in regions of endemicity in Africa and South America. Specific detection of vaccine-related adverse events is resource-intensive, time-consuming, and difficult to achieve during an outbreak. To address this, we have developed a highly transferable rapid yellow fever virus (YFV) vaccine-specific real-time reverse transcription-PCR (RT-PCR) assay that distinguishes vaccine from wild-type lineages. The assay utilizes a specific hydrolysis probe that includes locked nucleic acids to enhance specific discrimination of the YFV17D vaccine strain genome. Promisingly, sensitivity and specificity analyses reveal this assay to be highly specific to vaccine strain(s) when tested on clinical samples and YFV cell culture isolates of global origin. Taken together, our data suggest the utility of this assay for use in laboratories of varied capacity for the identification and differentiation of vaccine-related adverse events from wild-type infections of both African and South American origin.

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Infection of hepatocytes with 17-D vaccine-strain yellow fever virus induces a strong pro-inflammatory host response

Journal of General Virology ◽

10.1099/vir.0.031617-0 ◽

2011 ◽

Vol 92 (10) ◽

pp. 2262-2271 ◽

Cited By ~ 11

Author(s):

Sara E. Woodson ◽

Michael R. Holbrook

Keyword(s):

Yellow Fever ◽

Vaccine Strain ◽

Host Response ◽

Yellow Fever Virus ◽

Vaccine Virus ◽

Fever Virus ◽

Productive Infection ◽

Wild Type Virus ◽

Type Virus ◽

Wild Type

Yellow fever virus (YFV) causes serious disease in endemic areas of South America and Africa, even though a very well tolerated vaccine is available. YFV primarily targets the liver where as many as 80 % of hepatocytes may be involved during infection. The objective of this project was to compare and contrast the cytokine response from hepatocytes infected with either wild-type (Asibi) or vaccine (17-D-204) strains of YFV, with the goal of identifying responses that might be correlated with disease severity or vaccine efficacy. We report here that PH5CH8 hepatocytes support a productive infection with both wild-type and vaccine-strain YFV. Infection with either virus resulted in elevated expression of several pro- and anti-inflammatory cytokines [interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10 and tumour necrosis factor-α) with a corresponding increase in transcription. Hepatocytes infected with vaccine virus had a more profound response than did cells infected with wild-type virus. Pre-stimulation of hepatocytes with IL-6 resulted in reduced viral titres, elevated concentrations of cytokines released from Asibi virus-infected cells and improved cell viability in cells infected with 17-D virus. Data reported here suggest that 17-D virus stimulates an appropriate antiviral inflammatory response in hepatocytes, while Asibi virus can attenuate the host response. These data identify potential mechanisms that are associated with increased virulence in wild-type virus infections and also provide clues towards potential immune-response limitations that may be associated with vaccine-related adverse events.

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