Development of Chimpanzee Adenovirus-Vectored Vaccine Strategies Against Pulmonary Tuberculosis

Abstract

The immense global tuberculosis (TB) burden highlights the shortcomings of current vaccination and antibiotic regimens. Novel prophylactic TB vaccines that can either boost or replace BCG entirely remains an active area of research. Additionally, the success of current antibiotic therapies against TB is hindered by their complexity and duration, with large percentages of patients failing to complete treatment. Multi-armed approaches are required to properly and efficiently combat diseases. Besides prophylactic vaccines, development of therapeutic vaccine strategies as an adjunct to antibiotic treatment would represent another major step in TB control. To achieve such a goal, vaccines must consider the pathogen’s life cycle, the immunological responses which they drive, and the populations in which they will ultimately be administered. As such, the purpose of this dissertation is to utilize state-of-the-art molecular cloning techniques to construct novel chimpanzee adenovirus-vectored vaccines that provide prophylactic and therapeutic immunity against pulmonary TB. By considering different phases of the pathogen’s life cycle, we aim to select a collection of antigens that are protective, regardless of disease state. Development of such platforms would lay and bolster the groundwork for improved vaccine strategies against TB.