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

Abstract

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.

Identifying Key Drivers of Efficient B Cell Responses: On the Role of T Help, Antigen-Organization, and Toll-like Receptor Stimulation for Generating a Neutralizing Anti-Dengue Virus Response

“…The design of VLPs/nanoparticles may promote a more balanced Th1/Th2 cell response [ 242 , 244 ], which leads to balanced Ab subclass responses [ 55 , 56 , 59 , 164 ]. In the context of generating the dengue vaccine candidates, the versatility of the VLP platforms allows for the exploration of VLPs derived directly from DENV (DENV VLPs) [ 180 , 245 , 246 , 247 ] or the use of other viral CP-based VLPs from sources such as mammalian viruses [ 182 , 248 ], plant viruses [ 50 , 51 , 249 ], or bacteriophages [ 77 , 250 , 251 ]. Broad comparative studies across different platforms could provide insight into their respective strengths and limitations in vaccine development, anti-dengue efficacy and safety.…”

Outlining recent updates on influenza therapeutics and vaccines: A comprehensive review

“…Conjugation of M2e protein in enveloped VLPs that normally express either HA or NA or both and hence demonstrate excellent immunogenic profiles [115] . These VLP-based vaccines have exhibited better immune responses than whole inactivated virus particles since they lack the shielding impact of large proteins [116] , [117] . VLP-based vaccines have shown efficacy against diverse subtypes of influenza including H1N1, H3N2, and H5N1, but suffer from silent amino acid variations in different host species [118] .…”

Characterization of surface-exposed structural loops as insertion sites for foreign antigen delivery in calicivirus-derived VLP platform

“…There has been a great deal of research into alternative approaches that address those issues. Among others, nanoscale virus-like particles (VLPs), which showed several therapeutic, immunogenic, and diagnostic uses, are regarded as the most promising platform for vaccine development among subunit vaccines (Frietze et al, 2016;Ong et al, 2017;Castilho et al, 2022).…”