Virus-Like Particles (VLPs) as Important Tools for Flavivirus Vaccine Development

Flaviviruses, such as dengue, zika, yellow fever, West Nile, and Japanese encephalitis virus, are RNA viruses belonging to the Flaviviridae family (genus Flavivirus). They represent an important global health concern, since most areas of the world are endemic for at least one of these viruses. Although vaccines for five flaviviruses currently exist, there is a need for new vaccines to protect from established, emerging, and reemerging flaviviruses. Yellow fever vaccine shortages experienced in the last decade, combined with the risk of YFV spread to Asia and the restrictions of vaccine administration to certain population segments, show that even when a highly efficacious vaccine is available, new and improved vaccines might be needed. Virus-like particles (VLPs) are multiprotein structures that mimic the virus, but do not contain its genetic material. As such, VLPs have an excellent track record of strong immunogenicity and high safety, dating back to the introduction of the first recombinant hepatitis B vaccine in the 1980s. Flavivirus-like particles (FVLPs) have been extensively studied, especially for DENV, JEV, and ZIKV, and could give rise to next-generation recombinant subunit flavivirus vaccines based on VLPs incorporating molecular features intended to ensure high efficacy and minimize the risk of antibody-dependent enhancement (ADE) upon infection with other flaviviruses.