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

Nat Commun. 2021 Nov 18;12(1):6658. doi: 10.1038/s41467-021-26934-0.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Bacterial / immunology
  • BCG Vaccine / administration & dosage
  • BCG Vaccine / immunology
  • Humans
  • Immunogenicity, Vaccine
  • Mice
  • Mycobacterium bovis / immunology
  • Mycobacterium tuberculosis / immunology*
  • Th1 Cells / immunology
  • Th17 Cells / immunology
  • Tuberculosis / immunology
  • Tuberculosis / prevention & control*
  • Tuberculosis Vaccines / administration & dosage*
  • Tuberculosis Vaccines / immunology
  • Vaccination / methods*
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / immunology


  • Antigens, Bacterial
  • BCG Vaccine
  • Tuberculosis Vaccines
  • Vaccines, Subunit