Novel Methods of Augmenting Lung TB Immunity
Abstract
This application specifically addresses the Fiscal Year 2018 Peer Reviewed Medical Research Program Topic Area ?Tuberculosis,? and the Area of Encouragement ?Development of novel and/or innovative tuberculosis vaccines or optimization of current tuberculosis vaccines.? The World Health Organization reports that tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is the greatest killer worldwide due to a single infectious agent, ranking even above HIV/AIDS. TB is an airborne disease that infects the lungs. It can be spread via droplets when an infected individual, for example, coughs. Currently, this disease can be treated by four different antibiotics that are administered for a period of 6 months. TB strains that are resistant to the top two drugs have emerged and were responsible for the infection of 490,000 individuals in 2016. More alarmingly, 6.2% of those cases were infected with TB strains that are extensively drug resistant and resist to second-line drugs as well. Bacillus Calmette-Guerin (BCG) is the only vaccine available. This vaccine is effective at preventing serious TB in children, but does not reliably prevent disease in adults. Therefore, there is an urgent unmet need for tuberculosis vaccines that induce greater protection. To control TB infection and disease, we propose a ?prime-pull? approach using chemokines to recruit immune cells into the lungs. Chemokines act as biological signals to attract immune cells to specific areas. We hypothesize that delivery of specific chemokines into the lungs of mice after a systemic vaccination will ?pull? primed T cells into the lungs and thus provide protection against TB disease. We will first optimize the TB vaccine ?prime? and chemokine ?pull? method to effectively recruit immune cells into mouse lungs. We then will next vaccinate mice using this prime-pull approach and later challenge animals with virulent M. tuberculosis. We will measure TB-specific immunity in the lungs, as well as determine bacterial burdens at 1 month post-challenge to determine whether this approach improves TB vaccine effectiveness. Our results will have a direct application to developing immunotherapeutics for latent and active TB, and therefore effective control of tuberculosis. The studies will have high relevance to the general fields of vaccinology and immunotherapy as well, and could provide a new strategy for prevention or treatment of various infectious agents.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 05, 2019
- Source ID
- W81XWH1910117XX0
Entities
People
- Getahun Abate
Organizations
- Saint Louis University
- United States Army