scholarly journals Restricted replication and lysosomal trafficking of yellow fever 17D vaccine virus in human dendritic cells

2007 ◽  
Vol 88 (1) ◽  
pp. 148-156 ◽  
Author(s):  
Dupeh R. Palmer ◽  
Stefan Fernandez ◽  
John Bisbing ◽  
Kristina K. Peachman ◽  
Mangala Rao ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Yellow Fever ◽  
Virus Replication ◽  
Yellow Fever Virus ◽  
Vaccine Virus ◽  
Yellow Fever Vaccine ◽  
Effective Vaccine ◽  
Contributing Factors

The yellow fever virus attenuated 17D vaccine strain is a safe and effective vaccine and a valuable model system for evaluating immune responses against attenuated viral variants. This study compared the in vitro interactions of the commercially available yellow fever vaccine (YF-VAX), Dengue virus and the live-attenuated dengue vaccine PDK50 with dendritic cells (DCs), the main antigen-presenting cells at the initiation of immune responses. Similar to PDK50, infection with YF-VAX generated activated DCs; however, for YF-VAX, activation occurred with limited intracellular virus replication. The majority of internalized virus co-localized with endolysosomal markers within 90 min, suggesting that YF-VAX is processed rapidly in DCs. These results indicate that restricted virus replication and lysosomal compartmentalization may be important contributing factors to the success of the YF-VAX vaccine.

scholarly journals Yellow Fever Virus Down-Regulates mRNA Expression of SOCS1 in the Initial Phase of Infection in Human Cell Lines

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 802
Author(s):  
Michael B. Yakass ◽  
David Franco ◽  
Osbourne Quaye
Keyword(s):  
Mrna Expression ◽  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Expression Patterns ◽  
Fever Virus ◽  
Effective Vaccine ◽  
Interferon Β ◽  
Infected Cells ◽  
Insight Into

Flaviviruses are constantly evolving diverse immune evasion strategies, and the exploitation of the functions of suppressors of cytokine signalling (SOCS) and protein inhibitors of activated STATs (PIAS) to favour virus replication has been described for Dengue and Japanese encephalitis viruses but not for yellow fever virus (YFV), which is still of global importance despite the existence of an effective vaccine. Some mechanisms that YFV employs to evade host immune defence has been reported, but the expression patterns of SOCS and PIAS in infected cells is yet to be determined. Here, we show that SOCS1 is down-regulated early in YFV-infected HeLa and HEK 293T cells, while SOCS3 and SOCS5 are not significantly altered, and PIAS mRNA expression appears to follow a rise-dip pattern akin to circadian-controlled genes. We also demonstrate that YFV evades interferon-β application to produce comparable viral titres. This report provides initial insight into the in vitro expression dynamics of SOCS and PIAS upon YFV infection and a basis for further investigation into SOCS/PIAS expression and how these modulate the immune response in animal models.

scholarly journals Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses

2008 ◽  
Vol 205 (13) ◽  
pp. 3119-3131 ◽  
Author(s):  
Denis Gaucher ◽  
René Therrien ◽  
Nadia Kettaf ◽  
Bastian R. Angermann ◽  
Geneviève Boucher ◽  
...  
Keyword(s):  
Immune Response ◽  
Transcription Factors ◽  
Immune Responses ◽  
Yellow Fever ◽  
Cell Response ◽  
T Cell Response ◽  
Yellow Fever Vaccine ◽  
Effector Cells ◽  
Polychromatic Flow Cytometry

Correlates of immune-mediated protection to most viral and cancer vaccines are still unknown. This impedes the development of novel vaccines to incurable diseases such as HIV and cancer. In this study, we have used functional genomics and polychromatic flow cytometry to define the signature of the immune response to the yellow fever (YF) vaccine 17D (YF17D) in a cohort of 40 volunteers followed for up to 1 yr after vaccination. We show that immunization with YF17D leads to an integrated immune response that includes several effector arms of innate immunity, including complement, the inflammasome, and interferons, as well as adaptive immunity as shown by an early T cell response followed by a brisk and variable B cell response. Development of these responses is preceded, as demonstrated in three independent vaccination trials and in a novel in vitro system of primary immune responses (modular immune in vitro construct [MIMIC] system), by the coordinated up-regulation of transcripts for specific transcription factors, including STAT1, IRF7, and ETS2, which are upstream of the different effector arms of the immune response. These results clearly show that the immune response to a strong vaccine is preceded by coordinated induction of master transcription factors that lead to the development of a broad, polyfunctional, and persistent immune response that integrates all effector cells of the immune system.

scholarly journals AT-752, a double prodrug of a guanosine nucleotide analog, inhibits yellow fever virus in a hamster model

2021 ◽  
Author(s):  
Kai Lin ◽  
Steven S Good ◽  
Justin G. Julander ◽  
Abbie Weight ◽  
Adel Moussa
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Limit Of Detection ◽  
Virus Titer ◽  
Fever Virus ◽  
Effective Vaccine ◽  
Hamster Model ◽  
Nucleotide Analog

Yellow fever virus (YFV) is a zoonotic pathogen re-emerging in parts of the world, causing a viral hemorrhagic fever associated with high mortality rates. While an effective vaccine is available, having an effective antiviral against YFV is critical against unexpected outbreaks, or when vaccination is not recommended. We have previously identified AT-281, the free base of AT-752, an orally available double prodrug of a guanosine nucleotide analog, as a potent inhibitor of YFV in vitro , with a 50% effective concentration (EC 50 ) of 0.31 µM. In hamsters infected with YFV (Jimenez strain), viremia rose about 4 log 10 -fold and serum alanine aminotransferase (ALT) 2-fold compared to sham-infected animals. Treatment with 1000 mg/kg AT-752 for 7 days, initiated 4 h prior to viral challenge, reduced viremia to below the limit of detection by day 4 post infection (pi) and returned ALT to normal levels by day 6 pi. When treatment with AT-752 was initiated 2 days pi, the virus titer and ALT dropped >2 log 10 and 53% by day 4 and 6 pi, respectively. In addition, at 21 days pi, 70 – 100% of the infected animals in the treatment groups survived compared to 0% of the untreated group (p<0.001). Moreover, in vivo formation of the active triphosphate metabolite AT-9010 was measured in the animal tissues, with the highest concentrations in liver and kidney, organs that are vulnerable to the virus. The demonstrated in vivo activity of AT-752 suggests that it is a promising compound for clinical development in the treatment of YFV infection.

RNA interference inhibits yellow fever virus replication in vitro and in vivo

Virus Genes ◽  
2009 ◽  
Vol 38 (2) ◽  
pp. 224-231 ◽  
Author(s):  
Carolina C. Pacca ◽  
Adriana A. Severino ◽  
Adriano Mondini ◽  
Paula Rahal ◽  
Solange G. P. D’avila ◽  
...  
Keyword(s):  
Rna Interference ◽  
Yellow Fever ◽  
Virus Replication ◽  
Yellow Fever Virus ◽  
Fever Virus

A Derivate of the Antibiotic Doxorubicin Inhibits Dengue and Yellow Fever Virus Replication In Vitro

2008 ◽  
Vol 78 (2) ◽  
pp. A33
Author(s):  
Suzanne Kaptein ◽  
Michael Jacobs ◽  
Andrea Gamarnik ◽  
Erik De Clercq ◽  
Ferenc Sztaricskai ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Virus Replication ◽  
Yellow Fever Virus ◽  
Fever Virus

scholarly journals Experimental DNA-Launched Live-Attenuated Vaccines Against Yellow Fever

2019 ◽  
Vol 18 (1) ◽  
pp. 18-25 ◽  
Author(s):  
P. Pushko ◽  
А. А. Ishmukhametov ◽  
P. P. Bredenbeek ◽  
I. S. Lukashevich
Keyword(s):  
Immune Responses ◽  
Dna Vaccine ◽  
Yellow Fever ◽  
Vaccine Virus ◽  
Genomic Rna ◽  
Dna Encoding ◽  
Live Attenuated Vaccine ◽  
Pathogenic Virus

Background DNA-launched vaccine is “manufactured” in vaccinated individuals and does not require traditional vaccine manufacturing facility and technology. Goals. Using yellow fever 17D vaccine, we have provided proof-of-concept evidence that these vaccine can be launched from DNA and induce specific immune responses against pathogenic virus causing yellow fever. The infectious DNA vaccine technology is based on the transcription of the full-length genomic RNA of the live-attenuated virus from plasmid DNA in vitro and in vivo. A few ng of infectious DNA encoding the fulllength genomic RNA are required to initiate the replication of the vaccine virus in vitro. The in vivo-generated viral RNA initiates limited replication of the vaccine virus, which in turn leads to efficient immunization. Electroporation in vivo has induced specific immune responses against pathogenic virus and protected mice against fatal disease. Here we describe a novel infectious DNA vaccine technology which combines advantages of naked DNA vaccination and live-attenuated vaccine efficacy. Conclusions If successful in further testing, this technology can dramatically change the way we make vaccines as well as vaccination practice. 

scholarly journals Disease Resurgence, Production Capability Issues and Safety Concerns in the Context of an Aging Population: Is There a Need for a New Yellow Fever Vaccine?

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 179 ◽  
Author(s):  
Kay M. Tomashek ◽  
Mark Challberg ◽  
Seema U. Nayak ◽  
Helen F. Schiltz
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Virus Transmission ◽  
Viral Disease ◽  
Yellow Fever Vaccine ◽  
Effective Vaccine ◽  
Level Of Concern ◽  
Endemic Areas ◽  
And Control ◽  
Agent Development

Yellow fever is a potentially fatal, mosquito-borne viral disease that appears to be experiencing a resurgence in endemic areas in Africa and South America and spreading to non-endemic areas despite an effective vaccine. This trend has increased the level of concern about the disease and the potential for importation to areas in Asia with ecological conditions that can sustain yellow fever virus transmission. In this article, we provide a broad overview of yellow fever burden of disease, natural history, treatment, vaccine, prevention and control initiatives, and vaccine and therapeutic agent development efforts.

scholarly journals Yellow Fever Vaccine Protects Resistant and Susceptible Mice Against Zika Virus Infection

2019 ◽  
Author(s):  
Ana C. Vicente Santos ◽  
Francisca H. Guedes-da-Silva ◽  
Carlos H. Dumard ◽  
Vivian N. S. Ferreira ◽  
Igor P. S. da Costa ◽  
...  
Keyword(s):  
Viral Load ◽  
Virus Infection ◽  
Yellow Fever ◽  
Zika Virus ◽  
Large Scale ◽  
Yellow Fever Virus ◽  
Yellow Fever Vaccine ◽  
Effective Vaccine ◽  
Type I ◽  
Zika Virus Infection

AbstractZika virus (ZIKV) emerged as an important infectious disease agent in Brazil in 2016. Infection usually leads to mild symptoms but severe congenital neurological disorders and Guillain-Barré syndrome have been reported following ZIKV exposure. The development of an effective vaccine against Zika virus is a public health priority, encouraging the preclinical and clinical studies of different vaccine strategies. Here, we describe the protective effect of an already licensed attenuated yellow fever vaccine (17DD) on type-I interferon receptor knockout mice (A129) and immunocompetent (BALB/c) mice infected with ZIKV. Yellow fever virus vaccination results in robust protection against ZIKV, with decreased mortality in the A129 mice, a reduction in the cerebral viral load in all mice, and weight loss prevention in the BALB/c mice. Despite the limitation of yellow fever (17DD) vaccine to elicit antibody production and neutralizing activity against ZIKV, we found that YF immunization prevented the development of neurological impairment induced by intracerebral virus inoculation in adult. Although we used two vaccine doses in our protocol, a single dose was protective, reducing the cerebral viral load. Different Zika virus vaccine models have been tested; however, our work shows that an efficient and certified vaccine, available for use for several decades, effectively protects mice against Zika virus infection. These findings open the possibility for using an available and inexpensive vaccine to a large-scale immunization in the event of a Zika virus outbreak.

scholarly journals Yellow Fever Outbreak in Eastern Senegal, 2020–2021

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1475
Author(s):  
Moussa Moïse Diagne ◽  
Marie Henriette Dior Ndione ◽  
Alioune Gaye ◽  
Mamadou Aliou Barry ◽  
Diawo Diallo ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Mosquito Species ◽  
Virus Transmission ◽  
Genomic Analysis ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
World Health ◽  
Effective Vaccine ◽  
Ministry Of Health

Yellow fever virus remains a major threat in low resource countries in South America and Africa despite the existence of an effective vaccine. In Senegal and particularly in the eastern part of the country, periodic sylvatic circulation has been demonstrated with varying degrees of impact on populations in perpetual renewal. We report an outbreak that occurred from October 2020 to February 2021 in eastern Senegal, notified and managed through the synergistic effort yellow fever national surveillance implemented by the Senegalese Ministry of Health in collaboration with the World Health Organization, the countrywide 4S network set up by the Ministry of Health, the Institut Pasteur de Dakar, and the surveillance of arboviruses and hemorrhagic fever viruses in human and vector populations implemented since mid 2020 in eastern Senegal. Virological analyses highlighted the implication of sylvatic mosquito species in virus transmission. Genomic analysis showed a close relationship between the circulating strain in eastern Senegal, 2020, and another one from the West African lineage previously detected and sequenced two years ago from an unvaccinated Dutch traveler who visited the Gambia and Senegal before developing signs after returning to Europe. Moreover, genome analysis identified a 6-nucleotide deletion in the variable domain of the 3′UTR with potential impact on the biology of the viral strain that merits further investigations. Integrated surveillance of yellow fever virus but also of other arboviruses of public health interest is crucial in an ecosystem such as eastern Senegal.

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