AUTHOR=Fiore-Gartland Andrew , Srivastava Himangi , Seese Aaron , Day Tracey , Penn-Nicholson Adam , Luabeya Angelique Kany Kany , Du Plessis Nelita , Loxton Andre G. , Bekker Linda-Gail , Diacon Andreas , Walzl Gerhard , Sagawa Zachary K. , Reed Steven G. , Scriba Thomas J. , Hatherill Mark , Coler Rhea TITLE=Co-regulation of innate and adaptive immune responses induced by ID93+GLA-SE vaccination in humans JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1441944 DOI=10.3389/fimmu.2024.1441944 ISSN=1664-3224 ABSTRACT=Introduction

Development of an effective vaccine against tuberculosis is a critical step towards reducing the global burden of disease. A therapeutic vaccine might also reduce the high rate of TB recurrence and help address the challenges of drug-resistant strains. ID93+GLA-SE is a candidate subunit vaccine that will soon be evaluated in a phase 2b efficacy trial for prevention of recurrent TB among patients undergoing TB treatment. ID93+GLA-SE vaccination was shown to elicit robust CD4+ T cell and IgG antibody responses among recently treated TB patients in the TBVPX-203 Phase 2a study (NCT02465216), but the mechanisms underlying these responses are not well understood.

Methods

In this study we used specimens from TBVPX-203 participants to describe the changes in peripheral blood gene expression that occur after ID93+GLA-SE vaccination.

Results

Analyses revealed several distinct modules of co-varying genes that were either up- or down-regulated after vaccination, including genes associated with innate immune pathways at 3 days post-vaccination and genes associated with lymphocyte expansion and B cell activation at 7 days post-vaccination. Notably, the regulation of these gene modules was affected by the dose schedule and by participant sex, and early innate gene signatures were correlated with the ID93-specific CD4+ T cell response.

Discussion

The results provide insight into the complex interplay of the innate and adaptive arms of the immune system in developing responses to vaccination with ID93+GLA-SE and demonstrate how dosing and schedule can affect vaccine responses.