Flavivaccine encompasses the entire research and development process to create a safe and cost-effective vaccine against multiple flaviviruses.
Due to the wide geographic distribution of Aedes and Culex mosquitoes, almost all the human population is at risk of flavivirus infection. In fact, mosquitoes, known for their preference for warmer climates, have in recent years been moving further north in Europe and North America, which were once too cold for them to thrive.
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Faced with the challenges to control the growing and expanding mosquito population (or vector), models that consider increased urbanisation, global transportation, and climate change predict further aggravation and expansion of the public health, economic and social burdens associated with mosquito-borne illnesses.
Our project focuses on combating the global threat from flaviviruses including but not limited to dengue, yellow fever, Zika, and West Nile. However, Flavivaccine can potentially protect against other flaviviruses including Japanese Encephalitis.
While effective vaccines exist for yellow fever (of note, the live-attenuated yellow fever vaccine, YF-VX, is currently in global shortage) and Japanese encephalitis, developing vaccines against the other mosquito-borne flaviviruses is fraught with difficulties. The immune response required to provide protection without causing enhancement of the disease is intricate. For example, in the case of dengue, exposure to one of the virus’s four serotypes can increase the risk of severe disease upon subsequent infection with another serotype—a phenomenon known as antibody-dependent enhancement (ADE).
Flaviviruses, characterised by their single-stranded RNA structure, are particularly prone to mutations, which enhances their ability to jump from one host species to another. This biological propensity for change, combined with extensive animal reservoirs and the expanding habitats of their vectors (such as mosquitoes and ticks), creates an ideal condition for the emergence of new flaviviruses.
The dengue virus encompasses four distinct serotypes (DEN-1, DEN-2, DEN-3, and DEN-4) that can cause dengue fever. Infection with one serotype provides lifelong immunity to it but only short-term immunity to the others. Subsequent infections by other serotypes increase the risk of severe complications.
GLOBAL CASES | |
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390 milinfections per year | 100 milmanifesting clinically |
SYMPTOMS | VECTOR |
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VACCINE |
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| Dengvaxia: it is available but recommended only for those who have previously been infected with dengue virus. It is a live recombinant tetravalent vaccine made using recombinant DNA technology. Qdenga: its effectiveness may not be equally robust across all serotypes: the current data appear to show only moderate efficacy in other dengue serotypes than DENV2 |
NOT SO FUN FACTS |
| The phenomenon of antibody-dependent enhancement (ADE) occurs when someone who has previously been infected with one of the four dengue virus serotypes gets infected a second time with a different serotype. Instead of providing immunity, the antibodies from the first infection can facilitate the entry of the new serotype into host cells, leading to a more severe form of the disease known as severe dengue or dengue haemorrhagic fever. This more severe form can cause plasma leakage, severe bleeding, and organ impairment, and can be life-threatening. |
It was first identified in Uganda in 1947 in monkeys and was later identified in humans in 1952. The 2015 Zika epidemic was a stark reminder of how quickly flaviviruses, previously of relative obscurity, can become significant public health threats. Prior to the outbreak in the Americas, Zika was a little-known virus causing only mild febrile illnesses in a limited number of people in Africa and parts of Asia.
GLOBAL CASES | |
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1.5 milpeople from 2014 | |
SYMPTOMS | VECTOR |
| No or mild symptoms. The most common are:
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VACCINE |
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| There is no vaccine for Zika virus as of the latest updates. Some clinical trials are ongoing. |
NOT SO FUN FACTS |
| Zika virus is associated with severe birth defects when pregnant women become infected. The most notable of these is microcephaly. |
Yellow fever is a viral haemorrhagic disease transmitted by infected mosquitoes found in tropical and subtropical areas of South America and Africa. The primary hosts of the yellow fever virus are non-human primates, typically monkeys living in the tropical rainforest areas. These primates act as the natural reservoirs of the virus.
GLOBAL CASES | |
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200,000infections | 30,000deaths each year (nearly 90% occurring in Africa) |
SYMPTOMS | VECTOR |
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VACCINE |
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| Yellow Fever Vaccine (YF-VAX): a live, attenuated vaccine offering effective immunity within 30 days for 99% of those vaccinated. |
NOT SO FUN FACTS |
| Yellow fever, despite being preventable with a highly effective vaccine, still causes an estimated 30,000 deaths worldwide each year, mostly in unvaccinated populations. Moreover, because it is live attenuated, the existing vaccine is not indicated in babies younger than 9 months old, in pregnant and breastfeeding women, in immunosuppressed patients, and in elderlies (older than 60 years of age for a prime injection). |
West Nile virus is mostly transmitted to humans through the bite of an infected mosquito. Birds are the natural hosts of the virus, serving as a reservoir from which mosquitoes can acquire the infection before passing it on to other birds, mammals, and humans.
GLOBAL CASES | |
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50,000people per year | 20% of symptomatic casesdebilitating and deadly neurological symptoms |
SYMPTOMS | VECTOR |
| 80% of infected people show no symptoms. When symptoms do occur, they can range from fever and body aches to severe neurologic illness. | Culex species of mosquitoes |
VACCINE |
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| No vaccine is available for humans. |
NOT SO FUN FACTS |
| West Nile virus has shown a remarkable ability to spread and establish itself in new geographical areas rapidly. For example, within just three years of its detection in New York in 1999, West Nile virus had spread throughout the continental United States, becoming a seasonal epidemic that flares up from July through October, peaking in August. |
Japanese encephalitis is found primarily in rural areas throughout Southeast Asia, the Pacific Islands, and the Far East. The virus primarily infects birds and pigs, but humans can become incidental hosts.
GLOBAL CASES | |
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30,000 to 50,000cases reported annually. | |
SYMPTOMS | VECTOR |
| Most infections are mild (fever and headache) or without apparent symptoms, but approximately 1 in 250 infections results in severe clinical illness which can include vomiting, disorientation, coma, and seizures | Culex species mosquitoes, especially Culex tritaenior hynchus |
VACCINE |
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| IXIARO (JEV): an inactivated vaccine approved for people 2 months of age and older. |
NOT SO FUN FACTS |
| Even after recovery from a Japanese encephalitis infection, approximately 30% to 50% of survivors suffer from significant neurologic, cognitive, or psychiatric sequelae. Many individuals who survive the acute phase of the infection may experience long-term complications such as paralysis, recurrent seizures, inability to speak, or emotional liability. |
Aside from those addressed here, several other flaviviruses, including Usutu, Rocio, Tembusu, and Spondweni viruses, are being closely monitored due to their potential to cause outbreaks. However, the true number of flaviviruses that could emerge and lead to epidemics is likely much higher, given the vast number of these viruses that remain uncharacterised in wild vertebrate populations. As the global landscape continues to change, our vaccination strategies must adapt to combat these changeable and often unpredictable viral foes.
