Abstract
Despite the availability of an effective, live attenuated yellow fever virus (YFV) vaccine (YFV 17D), this flavivirus still causes up to ≈60,000 deaths annually. A number of new approaches are seeking to address vaccine supply issues and improve safety for the immunocompromised vaccine recipients. Herein we describe an adult female IFNAR-/- mouse model of YFV 17D infection and disease that recapitulates many features of infection and disease in humans. We used this model to evaluate a new YFV vaccine that is based on a recently described chimeric Binjari virus (BinJV) vaccine technology. BinJV is an insect-specific flavivirus and the chimeric YFV vaccine (BinJ/YFV-prME) was generated by replacing the prME genes of BinJV with the prME genes of YFV 17D. Such BinJV chimeras retain their ability to replicate to high titers in C6/36 mosquito cells (allowing vaccine production), but are unable to replicate in vertebrate cells. Vaccination with adjuvanted BinJ/YFV-prME induced neutralizing antibodies and protected mice against infection, weight loss and liver pathology after YFV 17D challenge.
Highlights
Yellow fever virus (YFV) is endemic in 47 countries in Africa and Central and South America.During 2013 the virus caused 84,000–170,000 severe cases and 29,000–60,000 deaths globally [1].Large outbreaks have occurred in recent years in Angola, Democratic Republic of Congo and Brazil [2].A revised strategy to Eliminate Yellow Fever Epidemics (EYE) was launched by the World HealthOrganization (WHO) in 2017, with affordable vaccines and a sustained vaccine market representing key objectives [3,4]
We recently described a new chimeric flavivirus vaccine platform based on the insect specific flavivirus Binjari virus [24,25]
The BinJ/yellow fever virus (YFV)-prME chimera comprises a fully formed virus that is replication competent in C6/36 cells, it might be viewed as more of a virus-like particle (VLP)-like vaccine given that it is unable to replicate in vertebrate cells [24]
Summary
Yellow fever virus (YFV) is endemic in 47 countries in Africa and Central and South America.During 2013 the virus caused 84,000–170,000 severe cases and 29,000–60,000 deaths globally [1].Large outbreaks have occurred in recent years in Angola, Democratic Republic of Congo and Brazil [2].A revised strategy to Eliminate Yellow Fever Epidemics (EYE) was launched by the World HealthOrganization (WHO) in 2017, with affordable vaccines and a sustained vaccine market representing key objectives [3,4]. Yellow fever virus (YFV) is endemic in 47 countries in Africa and Central and South America. During 2013 the virus caused 84,000–170,000 severe cases and 29,000–60,000 deaths globally [1]. Large outbreaks have occurred in recent years in Angola, Democratic Republic of Congo and Brazil [2]. A revised strategy to Eliminate Yellow Fever Epidemics (EYE) was launched by the World Health. Organization (WHO) in 2017, with affordable vaccines and a sustained vaccine market representing key objectives [3,4]. Yellow fever (YF) is prevented by an effective live attenuated vaccine (17D), with a single dose able to confer life-long protection in most people. The global demand for YF vaccine supply has been estimated to be ≈102 million doses in 2016, and is expected to rise to ≈140 million doses in
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