Effect of Variations in BCG Vaccine Capsule Polysaccharides on Immunogenicity and Protective Efficacy
Abstract
This project sought to address 3 questions: 1) If genetically distinct BCG vaccine sub-strains, of which several are in use in different parts of the world, produce variable amounts of capsular polysaccharides. 2) If these variations correlate with differential activation of host innate and adaptive immune responses. 3)If the judicious changes to the growth culture media might impact the synthesis of these immune-active polysaccharides by BCG and might represent a simple way to enhance the immunogenic potential and protective efficacy of BCG vaccines. Our subsequent analyses revealed AM and DG production does indeed vary among different BCG sub-strains. We found non-treatment of BCG with detergents prior to interaction with macrophages interferes with invasion but is essential for the induction of inflammation. We observed that growth of BCG in 7H9, modified Sautons medium with low glycerol and its derivatives results in the increased production of AM in all BCG sub-strains while DG production is variably increased in most but not all BCG sub-strains. Interestingly, growth of BCG in 7H9 and low glycerol Sautons medium also enhances their ability to induce inflammation in macrophages although this varies greatly among different BCG sub-strains. However, we found no clear association between media-derived changes to AM and/or DG levels among BCG sub-strains with their capacity to induce inflammation in macrophages. These results suggest BCG cell-surface molecules other than CPs may be involved. In conclusion, the collective results from our work in this project indicate the relationship between BCG CP composition/abundance and the induction of host immune responses is far more complex than previously appreciated.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2021
- Accession Number
- AD1148564
Entities
People
- Jeffrey Chen
Organizations
- University of Saskatchewan