Progress and Works in Progress: Update on Flavivirus Vaccine Development

Abstract

Most areas of the globe are endemic for at least one flavivirus, putting billions at risk for infection. This diverse group of viral pathogens causes a range of manifestations in humans from asymptomatic infection to hemorrhagic fever to encephalitis to birth defects and even death. Many flaviviruses are transmitted by mosquitos and have expanded in geographic distribution in recent years, with dengue virus being the most prevalent, infecting approximately 400 million people each year. The explosive emergence of Zika virus in Latin America in 2014 refocused international attention on this medically important group of viruses. Meanwhile, yellow fever has caused major outbreaks in Africa and South America since 2015 despite a reliable vaccine. There is no vaccine for Zika yet, and the only licensed dengue vaccine performs suboptimally in certain contexts. Further lessons are found when considering the experience with Japanese encephalitis virus, West Nile virus, and tickborne encephalitis virus, all of which now have protective vaccination in human or veterinary populations. Thus, vaccination is a mainstay of public health strategy for combating flavivirus infections; however, numerous challenges exist along the path from development to delivery of a tolerable and effective vaccine. Nevertheless, intensification of investment and effort in this area holds great promise for significantly reducing the global burden of disease attributable to flavivirus infection.

Evaluation of the antiviral activity of orlistat (tetrahydrolipstatin) against dengue virus, Japanese encephalitis virus, Zika virus and chikungunya virus

“…Protective vaccination can offer a long-term solution to mosquito transmitted viruses, and effective, widely available vaccines are commercially available for JEV and YFV. However, these viruses remain the exception, and commercial vaccines for the other viruses in these two genera are either not yet available 36 or of uncertain broad utility 37 . However, the number of viruses in question make it www.nature.com/scientificreports www.nature.com/scientificreports/ unlikely that vaccines will be developed for all the pathogenic viruses in these two genera, and the potential for the emergence of viruses not previously considered a significant pathogen of concern (as exemplified by the sudden emergence of ZIKV 11 ) suggests that a reliance on vaccination alone is not a viable long term solution.…”

Immucillins in Infectious Diseases

“…Flavivirus infections alone cause an estimated 200 million clinical cases worldwide. 54 Subsequent studies demonstrated broad-specificity against both mosquito-borne and TBEV serocomplex flaviviruses with low or no toxicity against the mammalian host cells. 55 No incorporation into human RNA or DNA was detected.…”

Transcriptomic immune profiles of human flavivirus‐specific T‐cell responses

“…However, although it has been possible to develop efficient vaccinations for some members of the family (e.g. YFV, JEV), multiple factors are challenging the design of protective vaccination against WNV, DENV, and ZIKV . Among those, the viral variability has a considerable impact, and is particularly important in the case of DENV, where the co‐circulation of multiple serotypes with only 50%–60% homology leads to heterologous infections strongly associated with increased risk of severe DENV disease …”