Flavivirus
While endemic to the tropics, flaviviruses like Zika, dengue, West Nile or yellow fever virus are re-emerging pathogens of global health concern.
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Climate change and urbanization have largely contributed to the dissemination of the mosquito vector of flaviviruses, and Europe has in recent years been regularly confronted with autochthonous cases.
The genus flavivirus includes several human pathogens of medical importance (Zika, dengue, West Nile virus (WNV), and yellow fever virus). No specific antiviral therapies exist to treat flavivirus infection. Vaccination is currently the most effective instrument to control their circulation.
However, only a few licensed vaccines against flaviviruses are available on the market and some of them are limited to only a subset of the target human population (age limit, pregnancy, or immune status).
The yellow fever 17D (YF17D) vaccine has a unique track record of efficiency and safety.
Flaviviruses include pathogens of public health importance and are listed the HERA list of pathogens with high pandemic potential. They cause haemorrhagic, visceral, or neurological diseases and are responsible for many of the new or re-emerging viral epidemics. Although endemic in the tropical areas of the world, their spread to immunologically naïve populations is facilitated by climate changes and urbanisation, which has allowed the circulation of their mosquito vectors (especially Aedes aegypti, Aedes albopictus, and Culex pipiens) to new areas of the world, including Europe.
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Most recently, increasing numbers of autochthonous cases have been detected for dengue in France [PMID: 36330819] and WNV in Italy [PMID: 33923347; PMID: 36082685].
In addition to vector control strategies, vaccination is the most durable, efficient, and cost-effective solution to counteract the spreading of new or re-emerging flaviviruses.
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However, vaccine development is often based on an empirical approach, without mechanistic understanding of host-pathogen interactions. Although new advances in the field of reverse vaccinology have demonstrated the importance of antigen design [PMID: 24179220; PMID: 27022144; PMID: 30691364], our limited knowledge of the structure of immunogenic epitopes still impairs the ability to design new efficient vaccines rapidly and successfully. Ignorance on the features determining a protective epitope may result in the development of less efficient or even non-protective vaccines. For example, antigen prevalence in post-fusion conformation, as a result of the inactivation process, might explain the lower efficiency of the anti-SARS-CoV-2 vaccine Sinovac in generating neutralising antibodies [PMID: 34308395; PMID: 35365787].
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For flaviviruses, insufficient vaccine efficacy can even be a risk, as seen in Dengvaxia. This dengue vaccine heightens the risk of severe disease in naive recipients, likely due to antibody-dependent enhancement (ADE). As a result, it is now licensed solely for those with pre-existing dengue immunity [PMID: 31488666].