scholarly journals Yellow Fever Virus Genotyping Tool and Investigation of Suspected Adverse Events Following Yellow Fever Vaccination

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 206
Author(s):  
Izabela Maurício de Rezende ◽  
Pedro Augusto Alves ◽  
Matheus Soares Arruda ◽  
Andreza Parreiras Gonçalves ◽  
Gabriela Fernanda Garcia Oliveira ◽  
...  

The yellow fever (YF) vaccine consists of an attenuated virus, and despite its relative safety, some adverse events following YF vaccination have been described. At the end of 2016, Brazil experienced the most massive sylvatic yellow fever outbreak over the last 70 years and an intense campaign of YF vaccination occurred in Minas Gerais state in Southeast Brazil from 2016 to 2018. The present study aimed to develop a genotyping tool and investigate 21 cases of suspected adverse events following YF vaccination. Initial in silico analyses were performed using partial NS5 nucleotide sequences to verify the discriminatory potential between wild-type and vaccine viruses. Samples from patients were screened for the presence of the YFV RNA, using 5′UTR as the target, and then used for amplification of partial NS5 gene amplification, sequencing, and phylogenetic analysis. Genotyping indicated that 17 suspected cases were infected by the wild-type yellow fever virus, but four cases remained inconclusive. The genotyping tool was efficient in distinguishing the vaccine from wild-type virus, and it has the potential to be used for the differentiation of all yellow fever virus genotypes.

2018 ◽  
Vol 56 (6) ◽  
Author(s):  
Holly R. Hughes ◽  
Brandy J. Russell ◽  
Eric C. Mossel ◽  
John Kayiwa ◽  
Julius Lutwama ◽  
...  

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.


2011 ◽  
Vol 92 (10) ◽  
pp. 2262-2271 ◽  
Author(s):  
Sara E. Woodson ◽  
Michael R. Holbrook

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.


1992 ◽  
Vol 66 (7) ◽  
pp. 4265-4270 ◽  
Author(s):  
B K Sil ◽  
L M Dunster ◽  
T N Ledger ◽  
M R Wills ◽  
P D Minor ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Quinn DeGottardi ◽  
Theresa J. Gates ◽  
Junbao Yang ◽  
Eddie A. James ◽  
Uma Malhotra ◽  
...  

Abstract Monitoring the frequency of circulatory CXCR5+ (cCXCR5+) CD4+ T cells in periphery blood provides a potential biomarker to draw inferences about T follicular helper (TFH) activity within germinal center. However, cCXCR5+ T cells are highly heterogeneous in their expression of ICOS, PD1 and CD38 and the relationship between different cCXCR5 subsets as delineated by these markers remains unclear. We applied class II tetramer reagents and mass cytometry to investigate the ontogeny of different subsets of cCXCR5+ T cell following yellow fever immunization. Through unsupervised analyses of mass cytometry data, we show yellow fever virus-specific cCXCR5 T cells elicited by vaccination were initially CD38+ICOS+PD1+, but then transitioned to become CD38+ICOS−PD1+ and CD38−ICOS−PD1+ before coming to rest as a CD38−ICOS−PD1− subset. These results imply that most antigen-specific cCXCR5+ T cells, including the CD38−ICOS−PD1− CXCR5+ T cells are derived from the CXCR5+CD38+ICOS+PD1+ subset, the subset that most resembles preTFH/TFH in the germinal center.


2006 ◽  
Vol 8 (6) ◽  
pp. 1530-1538 ◽  
Author(s):  
Anabelle Lefeuvre ◽  
Hugues Contamin ◽  
Thierry Decelle ◽  
Christophe Fournier ◽  
Jean Lang ◽  
...  

2019 ◽  
Vol 25 (8) ◽  
pp. 1567-1570 ◽  
Author(s):  
Paula E.S. Marinho ◽  
Pedro P.M. Alvarenga ◽  
Ana P.C. Crispim ◽  
Talitah M.S. Candiani ◽  
Alice M. Alvarenga ◽  
...  

mBio ◽  
2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Maria Dolores Fernandez-Garcia ◽  
Laurent Meertens ◽  
Maxime Chazal ◽  
Mohamed Lamine Hafirassou ◽  
Ophélie Dejarnac ◽  
...  

ABSTRACTThe live attenuated yellow fever virus (YFV) vaccine 17D stands as a “gold standard” for a successful vaccine. 17D was developed empirically by passaging the wild-type Asibi strain in mouse and chicken embryo tissues. Despite its immense success, the molecular determinants for virulence attenuation and immunogenicity of the 17D vaccine are poorly understood. 17D evolved several mutations in its genome, most of which lie within the envelope (E) protein. Given the major role played by the YFV E protein during virus entry, it has been hypothesized that the residues that diverge between the Asibi and 17D E proteins may be key determinants of attenuation. In this study, we define the process of YFV entry into target cells and investigate its implication in the activation of the antiviral cytokine response. We found that Asibi infects host cells exclusively via the classical clathrin-mediated endocytosis, while 17D exploits a clathrin-independent pathway for infectious entry. We demonstrate that the mutations in the 17D E protein acquired during the attenuation process are sufficient to explain the differential entry of Asibi versus 17D. Interestingly, we show that 17D binds to and infects host cells more efficiently than Asibi, which culminates in increased delivery of viral RNA into the cytosol and robust activation of the cytokine-mediated antiviral response. Overall, our study reveals that 17D vaccine and Asibi enter target cells through distinct mechanisms and highlights a link between 17D attenuation, virus entry, and immune activation.IMPORTANCEThe yellow fever virus (YFV) vaccine 17D is one of the safest and most effective live virus vaccines ever developed. The molecular determinants for virulence attenuation and immunogenicity of 17D are poorly understood. 17D was generated by serially passaging the virulent Asibi strain in vertebrate tissues. Here we examined the entry mechanisms engaged by YFV Asibi and the 17D vaccine. We found the two viruses use different entry pathways. We show that the mutations differentiating the Asibi envelope (E) protein from the 17D E protein, which arose during attenuation, are key determinants for the use of these distinct entry routes. Finally, we demonstrate that 17D binds and enters host cells more efficiently than Asibi. This results in a higher uptake of viral RNA into the cytoplasm and consequently a greater cytokine-mediated antiviral response. Overall, our data provide new insights into the biology of YFV infection and the mechanisms of viral attenuation.


2012 ◽  
Vol 87 (6) ◽  
pp. 1112-1115 ◽  
Author(s):  
Katherine B. Gibney ◽  
Olga I. Kosoy ◽  
Marc Fischer ◽  
Srilatha Edupuganti ◽  
Robert S. Lanciotti ◽  
...  

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