English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Dengue viruses (DENV) infect 50-100 million people each year. The spread of DENV-associated infections is one of the most serious public health problems worldwide, as there is no widely available vaccine or specific therapeutic for DENV infections. To address this, we developed a novel tetravalent dengue vaccine utilizing virus-like particle (VLP) technology. We created recombinant DENV1-4 VLPs by co-expressing precursor membrane (prM) and envelope (E) proteins, with a F108A mutation in the fusion loop structure of E to increase the production of VLPs in mammalian cells. Immunization with DENV1-4 VLPs as individual, monovalent vaccines elicited strong neutralization activity against each DENV serotype in mice. When immunized as a tetravalent vaccine, DENV1-4 VLPs elicited high levels of neutralization activity against all four serotypes simultaneously. The neutralization antibody response induced by the VLPs was significantly higher than DNA or recombinant E proteins immunization. Moreover, antibody-dependent enhancement (ADE) was not observed against any serotype at 1:10 serum dilution. We also demonstrated that Zika virus (ZIKV) VLP production level was enhanced by introducing the same F108A mutation in ZIKV envelope protein. Taken together, these results suggest that our strategy for DENV VLP production is applicable to other flavivirus VLP vaccine development, due to the similarity in their viral structures and describes the promising development of an effective tetravalent vaccine against the prevalent flavivirus.Importance: The dengue virus poses one of the most serious public health problems worldwide, and the incidence of diseases caused by the virus has increased dramatically. Despite decades of effort, there is no effective treatment against dengue. A safe and potent vaccine against dengue is still needed. We have developed a novel tetravalent dengue vaccine using virus-like particle (VLP) technology, which is non-infectious as it lacks viral genome. Previous attempts by other groups with dengue virus VLPs resulted in generally poor yields. We found that a critical amino acid mutation in the envelope protein enhances the production of VLP. Our tetravalent vaccine elicited potent neutralizing antibody responses against all four serotypes. Our finding can also be applied to vaccine development against other flaviviruses, such as Zika virus or West Nile virus.

An Envelope-Modified Tetravalent Dengue Virus-Like-Particle Vaccine Has Implications for Flavivirus Vaccine Design