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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI135723-02
Application #
9604761
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Eichelberg, Katrin
Project Start
2017-11-23
Project End
2022-10-31
Budget Start
2018-11-01
Budget End
2019-10-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Wistar Institute
Department
Type
DUNS #
075524595
City
Philadelphia
State
PA
Country
United States
Zip Code
19104