Effect of Variations in BCG Vaccine Capsule Polysaccharides on Immunogenicity and Protective Efficacy
Abstract
This proposal addresses the Fiscal Year 2017 Peer Reviewed Medical Research Program topic areas of tuberculosis and vaccine development for infectious disease. Central Problem: Tuberculosis (TB) is an airborne bacterial infection that kills and sickens millions of people worldwide. The live BCG vaccine, which is a closely related but weakened form of the TB bacteria, has been used for almost 100 years to protect against TB. Unfortunately BCG has had a poor record of consistently protecting against the disease on a global scale. One possible reason for this inconsistency may lie in the fact that BCG vaccines used in different parts of the world harbor variations in their genetic make-up. Some of these differences map to genes involved in the production of sugars called capsular polysaccharides (CP) that coat the cells of mycobacteria (including the TB bacteria and BCG). Importantly, mycobacterial CP is known to be involved in the activation of the human immune system by mycobacteria. Whether these genetic differences affect CP in BCG, and as a consequence impact their ability to activate the immune system (immunogenicity), a property crucial to its function as a TB vaccine is not known. Recent research has also shown that the type of artificial growth media used to culture mycobacteria can also influence CP production. In the case of BCG, the type of growth media used to culture them can influence their effectiveness as vaccines. Whether this is CP-mediated in BCG is also not known. Innovation of the Idea: This research proposal will specifically address if the BCG strains in clinical use today have different CP levels or compositions thereof and if these correlate with their abilities to activate the immune system. This study will also address whether growth media known to enhance or lessen the effectiveness of BCG occurs through changes in CP. If so, this research will enable the identification of specific factors that one might incorporate into custom-designed media for preparing the most immunogenic BCG. Impact of Research: This study will help answer the long-standing question as to why some BCG strains are better than others and open new avenues for further research such as identifying the precise molecular basis responsible for the differences in CP in different BCG strains. On a practical level, the results obtained in this work will enable the selection and production of an urgently needed, standardized, and highly immunogenic BCG strain for worldwide use by public health agencies all over the world. The results will also identify the most suitable BCG strains for development into next-generation genetically enhanced BCG vaccines in the continuing fight against TB.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810075
Entities
People
- Jeffrey Chen
Organizations
- United States Army
- University of Saskatchewan