Based on a multitude of data there are several features desired in an HIV Vaccine immunogen. Such animmunogen should induce strong and broad humoral and cellular immunity. Furthermore, as HIV is ingeneral a sexually transmitted disease and the cells of the gut are preferentially targeted for viraldestruction, an immunogen should be capable of inducing in particular mucosal as well as systemic immuneresponses. Currently there is no approach that can be simply administered that induces such a response.This proposal will focus on the induction of mucosal immune responses through a systemic vaccinationstrategy. We believe that this proposal has important implications for the development of HIV vaccines.There are 3 highly interrelated and highly novel projects that comprise this program.Project 1 (D. Weiner) will test the hypothesis in rodent models that a systemic vaccination which redirects Tcells from mucosal sites to systemic sites in vivo can result in enhanced mucosal humoral and cellularimmunity.Project 2 (P. Marx) Will extend the studies and test the mucosal redirection hypothesis in the criticallyimportant the macaque model.Project 3 (M. Betts) Will test several hypotheses regarding the functional nature of the induced immuneresponses using the latest polyfunctional immune methods in both mice and macaques in concert withproject 1 and 2.Program Oversight is provided by an experienced Administrative Core (D. Weiner).
The specific Aims of theAdministrative core are:
Aim 1 : Administration and coordination of the entire program project.
Aim 2 :Organizing the Annual SAB meeting. A stellar Scientific Advisory Board will provide additional guidance anddirection to facilitate the success of the overallprogram.
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