Re-thinking yellow fever vaccines: fighting old foes with new generation vaccines

Abstract

Despite the existence of a highly efficient yellow fever vaccine, yellow fever reemergence throughout Africa and the Americas has put 900 million people in 47 countries at risk of contracting the disease. Although the vaccine has been key to controlling yellow fever epidemics, its live-attenuated nature comes with a range of contraindications that prompts advising against its administration to pregnant and lactating women, immunocompromised individuals, and those with hypersensitivity to chicken egg proteins. Additionally, large outbreaks have highlighted problems with insufficient vaccine supply, whereby manufacturers rely on slow traditional manufacturing processes that prevent them from ramping up production. These limitations have contributed to an inadequate control of yellow fever and have favored the pursuit of novel yellow fever vaccine candidates that aim to circumvent the licensed vaccine's restrictions. Here, we review the live-attenuated vaccine's limitations and explore the epitome of a yellow fever vaccine, whilst scrutinizing next-generation vaccine candidates.

Keywords: Yellow fever; disease control; emerging disease; global health; live-attenuated vaccine; vaccine contraindications; vaccine shortage; yellow fever next-generation vaccines; yellow fever vaccine.

Figure 1.

YF-LAV annual requirements to eliminate Yellow Fever. The World Health Organization suggests that a total of 138.4 million vaccine doses are required to eliminate Yellow Fever from Africa, Central, South America, and the Caribbean. However, the annual vaccine needs are significantly higher than the total production of all six manufacturers running at full capacity. Currently, an unmet requirement of 58.4 million doses remains per annum. In this graphic depiction of the annual vaccine needs each ‘syringe’ represents 1.3 million vaccine doses.

Figure 2.

Overlapping distribution of Yellow Fever virus and Aedes aegypti’s probability of occurrence. According to the World Health Organization 47 countries in Africa, and Central and South America are considered Yellow Fever endemic countries (Yellow). YF endemic areas are regions where Yellow Fever virus circulation has been reported in either sylvatic or urban cycles, and therefore hold a potential risk of Yellow Fever virus transmission. Transmission of YF in non-endemic areas can be perpetuated upon importation of a YF infected subject to a region endemic to Yellow Fever’s main vector, the Aedes aegypti mosquito. Extensive widespread of Aedes mosquitoes (Orange) and the upsurge in international human migration puts half of the world’s population at risk upon YF importation.