A Mycobacterium tuberculosis-specific subunit vaccine that provides synergistic immunity upon co-administration with Bacillus Calmette-Guérin

Joshua S. Woodworth; Helena Strand Clemmensen; Hannah Battey; Karin Dijkman; Thomas Lindenstrøm; Raquel Salvador Laureano; Randy Taplitz; Jeffrey Morgan; Claus Aagaard; Ida Rosenkrands; Cecilia S. Lindestam Arlehamn; Peter Andersen; Rasmus Mortensen

doi:10.1038/s41467-021-26934-0

A Mycobacterium tuberculosis-specific subunit vaccine that provides synergistic immunity upon co-administration with Bacillus Calmette-Guérin

Joshua S. Woodworth, Helena Strand Clemmensen, Hannah Battey, Karin Dijkman, Thomas Lindenstrøm, Raquel Salvador Laureano, Randy Taplitz, Jeffrey Morgan, Claus Aagaard, Ida Rosenkrands, Cecilia S. Lindestam Arlehamn, Peter Andersen, Rasmus Mortensen^*

^*Corresponding author af dette arbejde

Immunology

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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Abstract

Given the encouraging clinical results of both candidate subunit vaccines and revaccination with Bacillus Calmette-Guérin (BCG) against tuberculosis (TB), there is support for combining BCG and subunit vaccination for increased efficacy. BCG and Mycobacterium tuberculosis (Mtb) share ~98% of their genome and current subunit vaccines are almost exclusively designed as BCG boosters. The goal of this study is to design a TB subunit vaccine composed of antigens not shared with BCG and explore the advantages of this design in a BCG + subunit co-administration vaccine strategy. Eight protective antigens are selected to create an Mtb-specific subunit vaccine, named H107. Whereas traditional vaccines containing BCG-shared antigens exhibit in vivo cross-reactivity to BCG, H107 shows no cross-reactivity and does not inhibit BCG colonization. Instead, co-administering H107 with BCG leads to increased adaptive responses against both H107 and BCG. Importantly, rather than expanding BCG-primed T cells, H107 broadens the overall vaccine repertoire with new T cell clones and introduces ‘adjuvant-imprinted’ qualities including Th17 responses and less-differentiated Th1 cells. Collectively, these features of H107 are associated with a substantial increase in long-term protection.

Originalsprog	Engelsk
Artikelnummer	6658
Tidsskrift	Nature Communications
Vol/bind	12
Antal sider	13
ISSN	2041-1723
DOI	https://doi.org/10.1038/s41467-021-26934-0
Status	Udgivet - 2021

Bibliografisk note

Funding Information:
We thank the C013-404 study team for providing the clinical data on BCG and H4:IC31® and in particular Dereck Tait and Maria Lempicki (IAVI) for constructive discussions. We acknowledge the NIH Tetramer Core Facility for provision of I-Ab:ESAT-64-17 and I-Ad:TB10.473-88 and corresponding negative control tetramers I-Ab:hCLIP and I-Ad:hCLIP. We acknowledge Ming Lui Olsen, Camilla Haumann Rasmussen, Camilla Myhre Maymann, and Vivi Andersen for excellent technical assistance in the laboratory as well as the staff at the experimental animal facilities at Statens Serum Institut. This work was supported by the Lundbeck Foundation (R249-2017-851), the Independent Research Fund Denmark (DFF—7025-00106, DFF—7016-00310), and the National Institutes of Health/National Institute of Allergy and Infectious Diseases (Grant R01AI135721). CSLA: NIH contract 75N9301900067.

Publisher Copyright:
© 2021, The Author(s).

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10.1038/s41467-021-26934-0Licens: CC BY

A Mycobacterium tuberculosis-specific subunit vaccine that provides synergistic immunity upon co-administration with Bacillus Calmette-GuérinForlagets udgivne version, 2,1 MBLicens: CC BY

Citationsformater

Woodworth, J. S., Clemmensen, H. S., Battey, H., Dijkman, K., Lindenstrøm, T., Laureano, R. S., Taplitz, R., Morgan, J., Aagaard, C., Rosenkrands, I., Lindestam Arlehamn, C. S., Andersen, P., & Mortensen, R. (2021). A Mycobacterium tuberculosis-specific subunit vaccine that provides synergistic immunity upon co-administration with Bacillus Calmette-Guérin. Nature Communications, 12, [6658]. https://doi.org/10.1038/s41467-021-26934-0

A Mycobacterium tuberculosis-specific subunit vaccine that provides synergistic immunity upon co-administration with Bacillus Calmette-Guérin. / Woodworth, Joshua S.; Clemmensen, Helena Strand; Battey, Hannah; Dijkman, Karin; Lindenstrøm, Thomas; Laureano, Raquel Salvador; Taplitz, Randy; Morgan, Jeffrey; Aagaard, Claus; Rosenkrands, Ida; Lindestam Arlehamn, Cecilia S.; Andersen, Peter; Mortensen, Rasmus.

I: Nature Communications, Bind 12, 6658, 2021.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Woodworth, JS, Clemmensen, HS, Battey, H, Dijkman, K, Lindenstrøm, T, Laureano, RS, Taplitz, R, Morgan, J, Aagaard, C, Rosenkrands, I, Lindestam Arlehamn, CS, Andersen, P & Mortensen, R 2021, 'A Mycobacterium tuberculosis-specific subunit vaccine that provides synergistic immunity upon co-administration with Bacillus Calmette-Guérin', Nature Communications, bind 12, 6658. https://doi.org/10.1038/s41467-021-26934-0

Woodworth, Joshua S. ; Clemmensen, Helena Strand ; Battey, Hannah ; Dijkman, Karin ; Lindenstrøm, Thomas ; Laureano, Raquel Salvador ; Taplitz, Randy ; Morgan, Jeffrey ; Aagaard, Claus ; Rosenkrands, Ida ; Lindestam Arlehamn, Cecilia S. ; Andersen, Peter ; Mortensen, Rasmus. / A Mycobacterium tuberculosis-specific subunit vaccine that provides synergistic immunity upon co-administration with Bacillus Calmette-Guérin. I: Nature Communications. 2021 ; Bind 12.

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abstract = "Given the encouraging clinical results of both candidate subunit vaccines and revaccination with Bacillus Calmette-Gu{\'e}rin (BCG) against tuberculosis (TB), there is support for combining BCG and subunit vaccination for increased efficacy. BCG and Mycobacterium tuberculosis (Mtb) share ~98% of their genome and current subunit vaccines are almost exclusively designed as BCG boosters. The goal of this study is to design a TB subunit vaccine composed of antigens not shared with BCG and explore the advantages of this design in a BCG + subunit co-administration vaccine strategy. Eight protective antigens are selected to create an Mtb-specific subunit vaccine, named H107. Whereas traditional vaccines containing BCG-shared antigens exhibit in vivo cross-reactivity to BCG, H107 shows no cross-reactivity and does not inhibit BCG colonization. Instead, co-administering H107 with BCG leads to increased adaptive responses against both H107 and BCG. Importantly, rather than expanding BCG-primed T cells, H107 broadens the overall vaccine repertoire with new T cell clones and introduces {\textquoteleft}adjuvant-imprinted{\textquoteright} qualities including Th17 responses and less-differentiated Th1 cells. Collectively, these features of H107 are associated with a substantial increase in long-term protection.",

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AU - Lindenstrøm, Thomas

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