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

• Published in: Nature communications Vol. 12; no. 1; p. 6658
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.11.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/21; 13/31; 38/91; 631/250/255/1856; 631/250/590/2294; 64/60; 82/29; 82/80; 82/83; Animals; Antigens; Antigens, Bacterial - immunology; Bacillus; BCG Vaccine - administration & dosage; BCG Vaccine - immunology; Cell differentiation; Colonization; Cross-reactivity; Design; Genomes; Helper cells; Humanities and Social Sciences; Humans; Immunity; Immunogenicity, Vaccine; Lymphocytes; Lymphocytes T; Mice; multidisciplinary; Mycobacterium bovis - immunology; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; Science; Science (multidisciplinary); Th1 Cells - immunology; Th17 Cells - immunology; Tuberculosis; Tuberculosis - immunology; Tuberculosis - prevention & control; Tuberculosis Vaccines - administration & dosage; Tuberculosis Vaccines - immunology; Vaccination - methods; Vaccines; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - immunology
• ISSN: 2041-1723; 2041-1723
• 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. Tuberculosis (TB) subunit vaccines have been investigated as boosters for BCG-induced immunity. Here, the authors design a TB subunit vaccine that doesn't share antigens with BCG and show that co-administration of the two vaccines broadens the T cell response to TB and increases protection.