XXXX -expressed dengue 3 envelope-based virus-like particles elicit predominantly domain III-focused high titer neutralizing antibodies.

@entity4002 @entity66 @entity10056 @entity19 @entity734
Dengue poses a serious public health risk to nearly half the global population. It causes ~400 million infections annually and is considered to be one of the fastest spreading @entity4002 . Four distinct serotypes of dengue viruses (DENV-1, -2, -3, and -4) cause @entity66 , which may be either mild or extremely severe. @entity734 ( @entity734 ), by pre-existing cross-reactive antibodies, is considered to be the major mechanism underlying severe disease. This mandates that a preventive vaccine must confer simultaneous and durable immunity to each of the four prevalent DENV serotypes. Recently, we used @entity10056 , to express recombinant DENV-2 E ectodomain, and found that it assembled into virus-like particles (VLPs), in the absence of prM, implicated in the elicitation of @entity734 -mediating antibodies. These VLPs elicited predominantly type-specific neutralizing antibodies that conferred significant protection against lethal DENV-2 challenge, in a @entity19 model. The current work is an extension of this approach to develop prM-lacking DENV-3 E VLPs. Our data reveal that @entity10056 -produced DENV-3 E VLPs not only preserve the antigenic integrity of the major neutralizing epitopes, but also elicit potent DENV-3 virus-neutralizing antibodies. Further, these neutralizing antibodies appear to be exclusively directed toward domain III of the DENV-3 E VLPs. Significantly, they also lack discernible @entity734 potential toward heterotypic DENVs. Taken together with the high productivity of the @entity10056 expression system, this approach could potentially pave the way toward developing a DENV E-based, inexpensive, safe, and efficacious tetravalent sub-unit vaccine, for use in resource-poor dengue endemic countries.
