Immunization with Mycobacterium tuberculosis -Specific Antigens Bypasses T Cell Differentiation from Prior Bacillus Calmette-Guérin Vaccination and Improves Protection in Mice

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 phe...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2020-10, Vol.205 (8), p.2146-2155
Main Authors: Aagaard, Claus, Knudsen, Niels Peter Hell, Sohn, Iben, Izzo, Angelo A, Kim, Hongmin, Kristiansen, Emma Holsey, Lindenstrøm, Thomas, Agger, Else Marie, Rasmussen, Michael, Shin, Sung Jae, Rosenkrands, Ida, Andersen, Peter, Mortensen, Rasmus
Format: Article
Language:English
Subjects:
Animals
Antigens, Bacterial - immunology
Cell Differentiation - immunology
Female
Guinea Pigs
Immunotherapy and Vaccines
Mice
Mycobacterium bovis - immunology
Mycobacterium tuberculosis - immunology
T-Lymphocytes - immunology
T-Lymphocytes - pathology
Tuberculosis - immunology
Tuberculosis - pathology
Tuberculosis - prevention & control
Vaccination
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Summary: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 -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 -specific vaccine induced similar protection compared with the BCG boosting vaccine. However, in BCG-primed animals, only the -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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.2000563