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

doi:10.4049/jimmunol.2000563

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

Department of Microbiology

Research output: Contribution to journal › Article › peer-review

10 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 language	English
Pages (from-to)	2146-2155
Number of pages	10
Journal	Journal of Immunology
Volume	205
Issue number	8
DOIs	https://doi.org/10.4049/jimmunol.2000563
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.4049/jimmunol.2000563

Cite this

Aagaard, C., Hell Knudsen, N. P., Sohn, I., Izzo, A. A., Kim, H., Kristiansen, E. H., Lindenstrøm, T., Agger, E. M., Rasmussen, M., Shin, S. J., Rosenkrands, I., Andersen, P., & Mortensen, R. (2020). Immunization with mycobacterium tuberculosis–Specific antigens bypasses T cell differentiation from prior bacillus calmette–Guérin vaccination and improves protection in mice. Journal of Immunology, 205(8), 2146-2155. https://doi.org/10.4049/jimmunol.2000563

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title = "Immunization with mycobacterium tuberculosis–Specific antigens bypasses T cell differentiation from prior bacillus calmette–Gu{\'e}rin vaccination and improves protection in mice",

abstract = "Despite the fact that the majority of people in tuberculosis (TB)–endemic areas are vaccinated with the Bacillus Calmette–Gu{\'e}rin (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.",

author = "Claus Aagaard and {Hell Knudsen}, {Niels Peter} and Iben Sohn and Izzo, {Angelo A.} and Hongmin Kim and Kristiansen, {Emma Holsey} and Thomas Lindenstr{\o}m and Agger, {Else Marie} and Michael Rasmussen and Shin, {Sung Jae} and Ida Rosenkrands and Peter Andersen and Rasmus Mortensen",

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{\textquoteright}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{\textquoteright}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 {\textcopyright} 2020 by The American Association of Immunologists, Inc.",

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Aagaard, C, Hell Knudsen, NP, Sohn, I, Izzo, AA, Kim, H, Kristiansen, EH, Lindenstrøm, T, Agger, EM, Rasmussen, M, Shin, SJ, Rosenkrands, I, Andersen, P & Mortensen, R 2020, 'Immunization with mycobacterium tuberculosis–Specific antigens bypasses T cell differentiation from prior bacillus calmette–Guérin vaccination and improves protection in mice', Journal of Immunology, vol. 205, no. 8, pp. 2146-2155. https://doi.org/10.4049/jimmunol.2000563

Immunization with mycobacterium tuberculosis–Specific antigens bypasses T cell differentiation from prior bacillus calmette–Guérin vaccination and improves protection in mice. / Aagaard, Claus; Hell Knudsen, Niels Peter; Sohn, Iben et al.
In: Journal of Immunology, Vol. 205, No. 8, 15.10.2020, p. 2146-2155.

Research output: Contribution to journal › Article › peer-review

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AU - Izzo, Angelo A.

AU - Kim, Hongmin

AU - Kristiansen, Emma Holsey

AU - Lindenstrøm, Thomas

AU - Agger, Else Marie

AU - Rasmussen, Michael

AU - Shin, Sung Jae

AU - Rosenkrands, Ida

AU - Andersen, Peter

AU - Mortensen, Rasmus

N1 - 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.

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N2 - 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.

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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