Abstract
BackgroundDengue is today the most significant of arboviral diseases. Novel tools are necessary to effectively address the problem of dengue. Virus-like particles (VLP) offer a versatile nanoscale platform for developing tools with potential biomedical applications. From the perspective of a potentially useful dengue-specific tool, the dengue virus envelope protein domain III (EDIII), endowed with serotype-specificity, host receptor recognition and the capacity to elicit virus-neutralizing antibodies, is an attractive candidate.MethodsWe have developed a strategy to co-express and co-purify Hepatitis B virus surface (S) antigen in two forms: independently and as a fusion with EDIII. We characterized these physically and functionally.ResultsThe two forms of the S antigen associate into VLPs. The ability of these to display EDIII in a functionally accessible manner is dependent upon the relative levels of the two forms of the S antigen. Mosaic VLPs containing the fused and un-fused components in 1:4 ratio displayed maximal functional competence.ConclusionsVLPs armed with EDIII may be potentially useful in diagnostic, therapeutic and prophylactic applications.
Highlights
Dengue is today the most significant of arboviral diseases
We found that for Dengue virus (DENV)-2 envelope protein domain III (EDIII) to be displayed on the Virus-like particles (VLP) surface in way that made it accessible to DENV-2-specific antibody and to the host cell receptor, it was necessary to co-express the ES fusion antigen with un-fused S antigen
As the ES antigen by itself did not form VLPs efficiently, we attempted to co-express varying levels of un-fused S antigen as well
Summary
Dengue is today the most significant of arboviral diseases. Novel tools are necessary to effectively address the problem of dengue. Dengue represents the most important arboviral disease that places nearly half the global population at risk [1]. The mosquito-borne disease is caused by four closely related, yet antigenically distinct, serotypes of dengue viruses (DENV-1, -2, -3 and −4) [2]. All four DENVs and their mosquito vectors are co-prevalent in more than one hundred tropical/sub-tropical countries. Each of the DENVs can cause disease ranging from mild dengue fever to severe dengue hemorrhagic fever and potentially fatal dengue shock syndrome [3]. While increasingly reliable diagnostic tools are becoming available [4,5,6], antivirals [4,7,8] and vaccines [9,10] for dengue continue to be elusive
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