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 tomodulate this immunologic axis with vaccines designed to augment mucosal immunity. Our capacity to modulate cytokine profiles in the lung uniquelypositions us to test the effectiveness of prime-pull strategies for Mtb mucosal immunization. Our findings will be highly relevant for TB vaccinology. Inaddition, validating our new approach for TB may provide a more generalizable method to exploit targeted gene delivery and prime-pull for a wide range ofmucosal immunization contexts.Aim 1. Evaluate the effects on T cell recruitment of lung chemokine delivery during systemic TB vaccinationFirst, we will determine the kinetics of circulating mucosally relevant CXCR3+ T cells after BCG vaccination of wild type B6 mice. We next will optimize theprime-pull concept for TB vaccination and immunotherapy, comparing chemokine delivery methods, timing, and doses and their effects on lung T cellrecruitment.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 TBinfection. 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 challengedwith aerosolized M. tuberculosis. At 7-28 days after challenge, we will evaluate lung T cell responses and determine efficacy by enumerating mycobacteria inthe lungs and spleens.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2020
- Accession Number
- AD1110072
Entities
People
- Christopher Eickhoff
- Daniel Hoft
- David T. Curiel
- Elena Kashentseva
- Getahun Abate
- Igor Dmitriev
Organizations
- Saint Louis University
- Washington University in St. Louis