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

Author

Listed:
  • Joshua S. Woodworth

    (Statens Serum Institut)

  • Helena Strand Clemmensen

    (Statens Serum Institut
    Technical University of Denmark)

  • Hannah Battey

    (Statens Serum Institut)

  • Karin Dijkman

    (Statens Serum Institut)

  • Thomas Lindenstrøm

    (Statens Serum Institut)

  • Raquel Salvador Laureano

    (Statens Serum Institut)

  • Randy Taplitz

    (University of California San Diego)

  • Jeffrey Morgan

    (La Jolla Institute for Immunology)

  • Claus Aagaard

    (Statens Serum Institut)

  • Ida Rosenkrands

    (Statens Serum Institut)

  • Cecilia S. Lindestam Arlehamn

    (La Jolla Institute for Immunology)

  • Peter Andersen

    (Statens Serum Institut
    University of Copenhagen)

  • Rasmus Mortensen

    (Statens Serum Institut)

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.

Suggested Citation

  • Joshua S. Woodworth & Helena Strand Clemmensen & Hannah Battey & Karin Dijkman & Thomas Lindenstrøm & Raquel Salvador Laureano & Randy Taplitz & Jeffrey Morgan & Claus Aagaard & Ida Rosenkrands & Ceci, 2021. "A Mycobacterium tuberculosis-specific subunit vaccine that provides synergistic immunity upon co-administration with Bacillus Calmette-Guérin," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26934-0
    DOI: 10.1038/s41467-021-26934-0
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    References listed on IDEAS

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    1. Sudhasini Panda & Jeffrey Morgan & Catherine Cheng & Mayuko Saito & Robert H. Gilman & Nelly Ciobanu & Valeriu Crudu & Donald G. Catanzaro & Antonino Catanzaro & Timothy Rodwell & Judy S. B. Perera & , 2024. "Identification of differentially recognized T cell epitopes in the spectrum of tuberculosis infection," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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