AneffectiveTBvaccineremainsanelusivegoal.ThesuccessofBCGinpreventingdisseminatedTBsuggests thatitispossibletoprovidecompleteprotectionfrompulmonaryTBorTBinfectionthroughanimmunization strategy.However,thevaccine-inducedresponseselicitedbythemostrecentMVA85AphaseIIvaccinetrial weremodestandoflimiteddurabilitycomparedtoBCG.Theimmuneresponsesinducedinapreferredvaccine shouldalsobesuperiortothoseobservedusingBCGalone.Currently,thereisnosuchTBvaccineavailable, andfewgroupshavethecombinationoftechnologiesnowprovenintheclinictoproducesuchaplatform.This innovativeprogrammakesmajoradvancesinnewDNAadaptiveEP+geneadjvuantvaccinetechnologywhich intheclinicgeneratesTcellimmunityequivalentorsuperiortoliveviralvectorvaccines1,2.Wewillbuildonour recent clinical success by newer genetic adjuvants focused on improved T-cell and antibody induction. We concentrateonincreasingthebreadthofcoverageinducedbythesedesignedDNAvaccinebyexploringthe potential of a multivalent DNA vaccine targeting multiple Mtb antigens at both active and latent stages of TB infection.Furthermore,weplantodevelopthiscollectionoftechnologiesinasimplifiedvaccineschemethathas distinctclinicaladvantagesforglobaltesting.Therearethreeaimsthatcomprisethisprogramtoaddressthese issues.
ThereremainsapressingneedforaneffectiveTBvaccineandnocurrentvaccinetechnologyinducesstrong TH1 as well as humoral anti-Mtb immunity compared to Bacillus Calmette-Gurin (BCG). The goal of this programistoproduceanenhancedE/PdeliveredgeneadjuvantedDNAvaccine(E-DNA)potentiallycombined withaBCGprimeasavaccineplatform.Bythiscombination,wehypothesizethatwewillgenerateanimproved spectrumofTandBanti-MtbimmuneresponsescomparedtocurrentTBvaccinemodalitiesthatwouldrepresent amajoradvanceforTBvaccinedevelopment.
| Duperret, Elizabeth K; Liu, Shujing; Paik, Megan et al. (2018) A Designer Cross-reactive DNA Immunotherapeutic Vaccine that Targets Multiple MAGE-A Family Members Simultaneously for Cancer Therapy. Clin Cancer Res 24:6015-6027 |
