Yellow Fever

Yellow fever virus (YFV) is a mosquito-borne flavivirus that is the causative agent of yellow fever (YF), which is a disease that ranges in severity from an influenza-like syndrome to severe liver and renal dysfunction, circulatory shock, and hemorrhage. The disease causes substantial morbidity and mortality; case fatality rates often exceed 20% and, despite the availability of a vaccine, it is still a major public health problem for sub-Saharan Africa and tropical South America, and travelers to endemic areas. The virus is maintained in endemic areas of Africa and South America by enzootic transmission between mosquitoes and monkeys, and the epidemiology of the disease reflects the geographical distribution of the mosquito vectors. There are seven genotypes of this virus with five circulating in different geographic areas of Africa and two in South America. Two live-attenuated YF vaccines were simultaneously developed: the French neurotropic vaccine (FNV), or Dakar vaccine, and the 17D vaccine. In the 1980s the manufacture of FNV was completely discontinued because the World Health Organization (WHO) prohibited vaccination of children under 14 years old due to the high incidence of encephalitis. The development of the highly effective, live-attenuated 17D vaccine in the late 1930s is one of the milestones in vaccine research. The vaccine is safe and highly efficacious with one dose of vaccine giving immunity for at least 10 years, and may be lifelong immunity. Neutralizing antibodies are the correlate of protection. There are three substrains of the YF 17D vaccine in production today (17D-204, 17DD, and 17D-213). The WHO has standardized the seed lot and manufacturing processes, and published guidelines for approval of vaccine production and vaccination certificates. There are a number of contraindications for YF vaccination which include age, thymus disease, pregnancy, breast-feeding, immune suppression, and hypersensitivity to eggs. In recent years, a rare but significant number of severe adverse events have been reported involving vaccine-associated viscerotropic and neurotropic disease. Current vaccine development involves utilizing the 17D vaccine virus backbone, via infectious clone technology, to develop a variety of chimeric virus vaccines, some of which have reached clinical trials for human use.