Novel Methods of Augmenting Lung TB Immunity
Abstract
Effector T cells have been shown to be key mediators of immunologic responses to Mtb. This novel prime-pull approach provides a promising avenue to modulate this immunologic axis with vaccines designed to augment mucosal immunity. Our capacity to modulate cytokine profiles in the lung uniquely positions us to test the effectiveness of prime-pull strategies for Mtb mucosal immunization. Our findings will be highly relevant for TB vaccinology. In addition, validating our new approach for TB may provide a more generalizable method to exploit targeted gene delivery and prime-pull for a wide range of mucosal immunization contexts. Aim 1. Evaluate the effects on T cell recruitment of lung chemokine delivery during systemic TB vaccination. First, we will determine the kinetics of circulating mucosally relevant CXCR3 T cells after BCG vaccination of wild type B6 mice. We next will optimize the prime-pull concept for TB vaccination and immunotherapy, comparing chemokine delivery methods, timing, and doses and their effects on lung T cell recruitment. Aim 2. Evaluate the effects of lung chemokine delivery during BCG vaccination on Mtb infection and disease. After optimization of the prime-pull strategy for BCG vaccination determined in aim 1 we will test whether this method translates to better control of TB infection. Mice will be vaccinated with BCG and sub-groups of mice will be treated with CXCL9/10 proteins or genes. After 1-3 months, mice will be challenged with aerosolized M. tuberculosis. At 7-28 days after challenge, we will evaluate lung T cell responses and determine efficacy by enumerating mycobacteria in the lungs and spleens.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2021
- Accession Number
- AD1143203
Entities
People
- Christopher Eickhoff
- Daniel Hoft
- David T. Curiel
- Elena Kashentseva
- Getahun Abate
- Igor Mitriev
Organizations
- Saint Louis University