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The Present and Future of Yellow Fever Vaccines.

ABSTRACT: The disease yellow fever (YF) is prevented by a live-attenuated vaccine, termed 17D, which has been in use since the 1930s. One dose of the vaccine is thought to give lifelong (35+ years) protective immunity, and neutralizing antibodies are the correlate of protection. Despite being a vaccine-preventable disease, YF remains a major public health burden, causing an estimated 109,000 severe infections and 51,000 deaths annually. There are issues of supply and demand for the vaccine, and outbreaks in 2016 and 2018 resulted in fractional dosing of the vaccine to meet demand. The World Health Organization (WHO) has established the "Eliminate Yellow Fever Epidemics" (EYE) initiative to reduce the burden of YF over the next 10 years. As with most vaccines, the WHO has recommendations to assure the quality, safety, and efficacy of the YF vaccine. These require the use of live 17D vaccine only produced in embryonated chicken eggs, and safety evaluated in non-human primates only. Thus, any second-generation vaccines would require modification of WHO recommendations if they were to be used in endemic countries. There are multiple second-generation YF vaccine candidates in various stages of development that must be shown to be non-inferior to the current 17D vaccine in terms of safety and immunogenicity to progress through clinical trials to potential licensing. The historic 17D vaccine continues to shape the global vaccine landscape in its use in the generation of multiple licensed recombinant chimeric live vaccines and vaccine candidates, in which its structural protein genes are replaced with those of other viruses, such as dengue and Japanese encephalitis. There is no doubt that the YF 17D live-attenuated vaccine will continue to play a role in the development of new vaccines for YF, as well as potentially for many other pathogens.

SUBMITTER: Hansen CA

PROVIDER: S-EPMC8468696 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The global distribution of the yellow fever mosquito Aedes aegypti is the subject of considerable attention because of its pivotal role as a biological vector of several high profile disease pathogens including dengue, chikungunya, yellow fever, and Zika viruses. There is also a lot of interest in the projected future species' distribution. However, less effort has been focused on its historical distribution, which has changed substantially over the past 100 years, especially in southern Europe where it was once widespread, but largely disappeared by the middle of the 20th century. The present work utilises all available historical records of the distribution of Ae. aegypti in southern Europe, the Near East within the Mediterranean Basin and North Africa from the late 19th century until the 1960's to construct a spatial distribution model using matching historical climatic and demographic data. The resulting model was then implemented using current climate and demographic data to assess the potential distribution of the vector in the present. The models were rerun with several different assumptions about the thresholds that determine habitat suitability for Ae. aegypti. The historical model matches the historical distributions well. When it is run with current climate values, the predicted present day distribution is somewhat broader than it used to be particularly in north-west France, North Africa and Turkey. Though it is beginning to reappear in the eastern Caucasus, this 'potential' distribution clearly does not match the actual distribution of the species, which suggests some other factors are responsible for its absence. Future distributions based on the historical model also do not match future distributions derived from models based only on present day vector distributions, which predict little or no presence in the Mediterranean Region. At the same time, the vector is widespread in the USA which is predicted to consolidate its range there in future. This contradiction and the implication for possible re-invasion of Europe are discussed.

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The Present and Future of Yellow Fever Vaccines.

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