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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Microbial Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1441944
This article is part of the Research Topic Immune Mechanisms of Protection Against Mycobacterium tuberculosis View all 5 articles

Co-regulation of innate and adaptive immune responses induced by ID93+GLA-SE vaccination in humans

Provisionally accepted
Andrew Fiore-Gartland Andrew Fiore-Gartland 1*Himangi Srivastava Himangi Srivastava 1Aaron Seese Aaron Seese 1Tracey Day Tracey Day 2Adam Penn-Nicholson Adam Penn-Nicholson 3Angelique K. Luabeya Angelique K. Luabeya 4Nelita Du Plessis Nelita Du Plessis 5Andre G. Loxton Andre G. Loxton 5Linda-Gail Bekker Linda-Gail Bekker 6Andreas Diacon Andreas Diacon 7Gerhard Walzl Gerhard Walzl 5Zachary K. Sagawa Zachary K. Sagawa 8Steven G. Reed Steven G. Reed 9Thomas Scriba Thomas Scriba 4Mark Hatherill Mark Hatherill 4Rhea Coler Rhea Coler 10
  • 1 Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States
  • 2 Independent researcher, Leiden, Netherlands
  • 3 Foundation for Innovative New Diagnostics, Geneva, Geneva, Switzerland
  • 4 South African Tuberculosis Vaccine Initiative (SATVI), Cape Town, Western Cape, South Africa
  • 5 DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
  • 6 Desmond Tutu Health Foundation, Cape Town, South Africa
  • 7 TASK, Cape Town, South Africa
  • 8 Access to Advanced Health Institute, Seattle, California, United States
  • 9 HDT Biotech Corporation, Seattle, Washington, United States
  • 10 Seattle Children's Research Institute, Seattle, Washington, United States

The final, formatted version of the article will be published soon.

    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. 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. 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. 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.

    Keywords: Tuberculosis, Vaccines, Systems Immunology, Innate, RNA sequencing

    Received: 31 May 2024; Accepted: 02 Sep 2024.

    Copyright: © 2024 Fiore-Gartland, Srivastava, Seese, Day, Penn-Nicholson, Luabeya, Du Plessis, Loxton, Bekker, Diacon, Walzl, Sagawa, Reed, Scriba, Hatherill and Coler. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Andrew Fiore-Gartland, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.