Developing a common vaccine against dengue, yellow fever and Zika

Mosquito from the genera Aedes transmit flaviviruses that are responsible for an enormous public health burden worldwide. These diseases threaten half of the world human population. The most important are dengue, Zika and Yellow fever. Dengue viruses are the most prevalent and affect an estimated 390 million people per year. About 100 million develop symptomatic illness that results in a spectrum of clinical outcomes, with rare more severe cases including hypovolemic shock from uncompensated plasma leakage, internal haemorrhage, organ dysfunction or death. Yellow fever virus (YFV) gave its name to the genus and currently still affects 200,000 people per year. While YFV causes similar flu-like symptoms as DENV, its clinical outcome is more severe with about 30% case fatality rate for symptomatic patients. Zika virus (ZIKV) recently emerged as an epidemic virus, infecting 1.5 million people over the past 3 years. ZIKV infection is mostly asymptomatic to mild but can cause lifedebilitating neurological disorders in newborns from infected mothers. The phenomenal increase in flavivirus prevalence in the past decades is caused by urbanization, international transportation and climate change, all facilitating mosquito transmission. With these aggravating factors unlikely to recede, flavivirus epidemics will most probably connue on this upward trend. There are no curative treatment against flavivirus diseases and only one efficient vaccine against YFV. The recent DENGVAXIA® vaccine against DENV has variable and poor efficacy against the different serotypes, is not recommended to protect against primo infection and is not licensed for young and old patients, which are the most vulnerable to dengue. Vector control is currently the main intervention to mitigate epidemics. However, these methods do not suffice to curb the on-going flavivirus emergence. Novel tools and especially a pan-flaviviral vaccine are urgently needed to prevent further damage to the world public health. Our team recently idenfied a potential vaccine target that could prevent infection by all flaviviruses. During mosquito transmission, the mosquito saliva contains viruses that are released during biting. These viruses then infect skin cells at the biting site before spreading throughout the body, causing systemic infection and the symptoms. We discovered a viral transmission enhancer in mosquito saliva that is common to all flaviviruses. Indeed, flaviviruses secrete in mosquito saliva a non-coding RNA that inhibits human innate immunity and, thus, increases infection at the biting site. The weakest stage of flavivirus life cycle is the initiation of infection during mosquito transmission. Only a few hundred viruses are secreted by the mosquito. For this reason, targeting the salivary infection enhancer that we discovered represents a promising vaccine target. The final global aim is to develop a vaccine against this novel transmission enhancer present in mosquito saliva after the full characterisation of this new viral strategy.