An effective TB vaccine remains an elusive goal. The success of BCG in preventing disseminated TB suggests that it is possible to provide complete protection from pulmonary TB or TB infection through an immunization strategy. However, the vaccine-induced responses elicited by the most recent MVA85A phase II vaccine trial were modest and of limited durability compared to BCG. The immune responses induced in a preferred vaccine should also be superior to those observed using BCG alone. Currently, there is no such TB vaccine available, and few groups have the combination of technologies now proven in the clinic to produce such a platform. This innovative program makes major advances in new DNA adaptive EP + gene adjvuant vaccine technology which in the clinic generates T cell immunity equivalent or superior to live viral vector vaccines. We will build on our recent clinical success by newer genetic adjuvants focused on improved T-cell and antibody induction. We concentrate on increasing the breadth of coverage induced by these designed DNA vaccine by exploring the potential of a multivalent DNA vaccine targeting multiple Mtb antigens at both active and latent stages of TB infection. Furthermore, we plan to develop this collection of technologies in a simplified vaccine scheme that has distinct clinical advantages for global testing. There are three aims that comprise this program to address these issues.
There remains a pressing need for an effective TB vaccine and no current vaccine technology induces strong TH1 as well as humoral anti-Mtb immunity compared to Bacillus Calmette-Gurin (BCG). The goal of this program is to produce an enhanced E/P delivered gene adjuvanted DNA vaccine (E-DNA) potentially combined with a BCG prime as a vaccine platform. By this combination, we hypothesize that we will generate an improved spectrum of T and B anti-Mtb immune responses compared to current TB vaccine modalities that would represent a major advance for TB vaccine development.
|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|