Journal
VACCINES
Volume 8, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/vaccines8030368
Keywords
yellow fever virus; mouse model; vaccine; Binjari virus
Categories
Funding
- Australian Postgraduate Award
- National Health and Medical Research Council (NHMRC) of Australia [APP1173880]
- NHMRC Development Grant [APP1178896]
- Australian Infectious Disease Research Centre, which is Centre of Excellence within the Global Virus Network
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Despite the availability of an effective, live attenuated yellow fever virus (YFV) vaccine (YFV 17D), this flavivirus still causes up to approximate 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.
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