{"id":28,"date":"2017-02-03T22:18:46","date_gmt":"2017-02-03T22:18:46","guid":{"rendered":"http:\/\/labs.icahn.mssm.edu\/zolla-paznerlab\/?page_id=28"},"modified":"2017-05-23T17:09:17","modified_gmt":"2017-05-23T17:09:17","slug":"projects","status":"publish","type":"page","link":"https:\/\/labs.icahn.mssm.edu\/zolla-paznerlab\/projects\/","title":{"rendered":"Research Projects"},"content":{"rendered":"<h3>NIH Program Project Grant # P01 AI100151<\/h3>\n<p>Results of the RV144 HIV Vaccine Trial in Thai Adults demonstrated modest and transient protection against HIV-1 infection in healthy individuals. To improve the efficacy and duration of the antibody (Ab) response, better immunogens are required. We postulate that Abs induced by novel\u00a0vaccine constructs will have higher specific activity, with stronger Ab titers and, within the total Ab response,\u00a0a greater proportion of the Abs needed for protection. Such novel constructs, which could present viral\u00a0epitopes in a context other than that of the whole envelope (Env), may also obviate the problems of the\u00a0transient Ab response associated with whole Env. We and others have demonstrated that by focusing the Ab\u00a0response on V3, cross-clade neutralizing Abs are elicited that remain detectable more than\u00a01 year after immunization.<\/p>\n<p>Therefore, we are\u00a0extending the platform we previously developed for designing and developing\u00a0V3-scaffold immunogens in order to create and test new epitope-scaffold protein immunogens that will focus\u00a0the Ab response on 2 additional sites of vulnerability in the Env: the V2 loop and the cluster of quaternary\u00a0neutralizing epitopes (QNEs) composed of portions of V2 and V3.<\/p>\n<p>This HIV Research and Design (HIVRAD) Program Project Grant will be composed of:<\/p>\n<ul>\n<li><em>Project 1:<\/em> Vaccines to Induce Functional Abs Targeting the V2 Loop<\/li>\n<li><em>Project 2:<\/em> Rational Design of\u00a0Immunogens Targeting the HIV-1 V2\/V3 Quaternary Neutralizing Epitopes\n<ul>\n<li>Core A: Administrative Core<\/li>\n<li>Core B: Protein Production Core<\/li>\n<li>Core C: Animal Studies Core<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p style=\"padding-left: 30px\">The epitope-scaffold immunogens to\u00a0be developed can be used individually or in combination; they will constitute powerful new tools for inducing\u00a0broad and potent protective Abs. Many of the participants have worked together for &gt;20 years to develop\u00a0and characterize &gt;100 human mAbs to HIV and other pathogens. Recently, the team has worked\u00a0collaboratively and synergistically in preparing and analyzing &gt;25 crystals of monoclonal Abs (mAbs) and\u00a0mAb\/epitope complexes, developing DNA Env primes and epitope-scaffold immunogens, and performing\u00a0immunization experiments. Our experience places us in a strong position to extend our studies to epitopes\u00a0that only recently have been recognized as important for protection from HIV infection.<\/p>\n<p style=\"padding-left: 30px\">By the completion\u00a0of the proposed program, we plan to have identified epitope-targeting immunogens and\u00a0immunization protocols that will generate Abs with protective antiviral functions directed\u00a0specifically toward the conserved regions of the V2 loop and the V2\/V3 quaternary neutralizing\u00a0epitopes of HIV-1 gp120.<\/p>\n<p>&nbsp;<\/p>\n<h3><\/h3>\n","protected":false},"excerpt":{"rendered":"<p>NIH Program Project Grant # P01 AI100151 Results of the RV144 HIV Vaccine Trial in Thai Adults demonstrated modest and transient protection against HIV-1 infection in healthy individuals. To improve the efficacy and duration of the antibody (Ab) response, better immunogens are required. We postulate that Abs induced by novel\u00a0vaccine constructs will have higher specific [&hellip;]<\/p>\n","protected":false},"author":207,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"full-width.php","meta":{"footnotes":""},"class_list":["post-28","page","type-page","status-publish","hentry"],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/labs.icahn.mssm.edu\/zolla-paznerlab\/wp-json\/wp\/v2\/pages\/28","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/labs.icahn.mssm.edu\/zolla-paznerlab\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/labs.icahn.mssm.edu\/zolla-paznerlab\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/zolla-paznerlab\/wp-json\/wp\/v2\/users\/207"}],"replies":[{"embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/zolla-paznerlab\/wp-json\/wp\/v2\/comments?post=28"}],"version-history":[{"count":7,"href":"https:\/\/labs.icahn.mssm.edu\/zolla-paznerlab\/wp-json\/wp\/v2\/pages\/28\/revisions"}],"predecessor-version":[{"id":163,"href":"https:\/\/labs.icahn.mssm.edu\/zolla-paznerlab\/wp-json\/wp\/v2\/pages\/28\/revisions\/163"}],"wp:attachment":[{"href":"https:\/\/labs.icahn.mssm.edu\/zolla-paznerlab\/wp-json\/wp\/v2\/media?parent=28"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}