Immunization with mycobacterium tuberculosis–Specific antigens bypasses T cell differentiation from prior bacillus calmette–Guérin vaccination and improves protection in mice

Claus Aagaard, Niels Peter Hell Knudsen, Iben Sohn, Angelo A. Izzo, Hongmin Kim, Emma Holsey Kristiansen, Thomas Lindenstrøm, Else Marie Agger, Michael Rasmussen, Sung Jae Shin, Ida Rosenkrands, Peter Andersen, Rasmus Mortensen

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Despite the fact that the majority of people in tuberculosis (TB)–endemic areas are vaccinated with the Bacillus Calmette–Guérin (BCG) vaccine, TB remains the leading infectious cause of death. Data from both animal models and humans show that BCG and subunit vaccines induce T cells of different phenotypes, and little is known about how BCG priming influences subsequent booster vaccines. To test this, we designed a novel Mycobacterium tuberculosis–specific (or “non-BCG”) subunit vaccine with protective efficacy in both mice and guinea pigs and compared it to a known BCG boosting vaccine. In naive mice, this M. tuberculosis–specific vaccine induced similar protection compared with the BCG boosting vaccine. However, in BCG-primed animals, only the M. tuberculosis–specific vaccine added significantly to the BCG-induced protection. This correlated with the priming of T cells with a lower degree of differentiation and improved lung-homing capacity. These results have implications for TB vaccine design. The Journal of Immunology, 2020, 205: 2146–2155.

Original languageEnglish
Pages (from-to)2146-2155
Number of pages10
JournalJournal of Immunology
Volume205
Issue number8
DOIs
Publication statusPublished - 2020 Oct 15

Bibliographical note

Funding Information:
This work was supported by The Danish Research Council (DFF - 7016-00310), the National Institutes of Health/National Institute of Allergy and Infectious Diseases (Grant 1R01AI135721-01), the European Union?s Horizon 2020 Framework Programme for Research and Innovation under Grant Agreement 643381 as part of the TBVAC2020 Consortium, and the National Institutes of Health/National Institute of Allergy and Infectious Diseases program Advanced Small Animal Models for the Testing of Candidate Therapeutic and Preventative Interventions against Mycobacteria (HHSN272201000009I-003, Task Order 12) at Colorado State University.

Funding Information:
This work was supported by The Danish Research Council (DFF - 7016-00310), the National Institutes of Health/National Institute of Allergy and Infectious Diseases (Grant 1R01AI135721-01), the European Union’s Horizon 2020 Framework Programme for Research and Innovation under Grant Agreement 643381 as part of the TBVAC2020 Consortium, and the National Institutes of Health/National Institute of Allergy and Infectious Diseases program Advanced Small Animal Models for the Testing of Candidate Therapeutic and Preventative

Publisher Copyright:
Copyright © 2020 by The American Association of Immunologists, Inc.

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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