The newly emerged mosquito-borne Zika virus (ZIKV) strains pose a global challenge owing to its ability to cause microcephaly and neurological disorders. Several ZIKV vaccine candidates have been proposed, including inactivated and live attenuated virus vaccines, vector-based vaccines, DNA and RNA vaccines. These have been shown to be efficacious in preclinical studies in mice and nonhuman primates, but their use will potentially be a threat to immunocompromised individuals and pregnant women. Virus-like particles (VLPs) are empty particles composed merely of viral proteins, which can serve as a safe and valuable tool for clinical prevention and treatment strategies. In this study, we used a new strategy to produce ZIKV VLPs based on the baculovirus expression system and demonstrated the feasibility of their use as a vaccine candidate. The pre-membrane (prM) and envelope (E) proteins were co-expressed in insect cells and self-assembled into particles similar to ZIKV. We found that the ZIKV VLPs could be quickly and easily prepared in large quantities using this system. The VLPs were shown to have good immunogenicity in immunized mice, as they stimulated high levels of virus neutralizing antibody titers, ZIKV-specific IgG titers and potent memory T cell responses. Thus, the baculovirus-based ZIKV VLP vaccine is a safe, effective and economical vaccine candidate for use against ZIKV.
Emerging infectious diseases are major threats to human health. Most severe viral disease outbreaks occur in developing regions where health conditions are poor. With increased international travel and business, the possibility of eventually transmitting infectious viruses between different countries is increasing. The most effective approach in preventing viral diseases is vaccination. However, vaccines are not currently available for numerous viral diseases. Virus-like particles (VLPs) are engineered vaccine candidates that have been studied for decades. VLPs are constructed by viral protein expression in various expression systems that promote the selfassembly of proteins into structures resembling virus particles. VLPs have antigenicity similar to that of the native virus, but are non-infectious as they lack key viral genetic material. VLP vaccines have attracted considerable research interest because they offer several advantages over traditional vaccines. Studies have shown that VLP vaccines can stimulate both humoral and cellular immune responses, which may offer effective antiviral protection. Here we review recent developments with VLP-based vaccines for several highly virulent emerging or re-emerging infectious diseases. The infectious agents discussed include RNA viruses from different virus families, such as the Arenaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae, Paramyxoviridae, and Togaviridae families.
Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne viral disease of global concerns due to the increasing incidence and lack of effective treatments. The causative agent, CCHF virus (CCHFV), has been characterized for years; however, its tropism in cell lines of different host and tissue origins remains unclear. This study characterized the susceptibility of 16 human and 6 animal cell lines to CCHFV. Increased viral load and viral nucleoprotein expression, and productive CCHFV replication were detected in human vascular (HUVEC), renal (SW-13 and HEK-293), hepatic (Huh7), and cerebral (U-87 MG) cell lines, which were considered CCHFV-highly permissive cell lines. Renal cell lines derived from monkey and dog could also support CCHFV replication. This study evaluated the susceptibility of different cell lines to CCHFV and identified CCHFV-permissive cell lines. Our findings raise concerns regarding the use of cell lines in ex vivo studies of CCHFV and may have important implications for further fundamental research, which would promote understanding of CCHFV pathogenesis and transmission, as well as benefit designing strategies for disease prevention and control.
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