In-vivo expressed Mycobacterium tuberculosis antigens recognised in three mouse strains after infection and BCG vaccination

• Published in: npj vaccines Vol. 6; no. 1; p. 81
• Main Authors: Coppola, Mariateresa, Jurion, Fabienne, van den Eeden, Susan J. F., Tima, Hermann Giresse, Franken, Kees L. M. C., Geluk, Annemieke, Romano, Marta, Ottenhoff, Tom H. M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03-06-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/255/1856; 631/250/590/2294; Animal models; Antigens; Biomedical and Life Sciences; Biomedicine; Immunization; Infections; Infectious Diseases; Medical Microbiology; Public Health; Rodents; Tuberculosis; Vaccine; Vaccines; Virology
• ISSN: 2059-0105; 2059-0105
• DOI: 10.1038/s41541-021-00343-2

Novel tuberculosis (TB)-vaccines preferably should (i) boost host immune responses induced by previous BCG vaccination and (ii) be directed against
Mycobacterium tuberculosis
(
Mtb
) proteins expressed throughout the
Mtb
infection-cycle. Human
Mtb
antigen-discovery screens identified antigens encoded by
Mtb
-genes highly expressed during in vivo murine infection (IVE-TB antigens). To translate these findings towards animal models, we determined which IVE-TB-antigens are recognised by T-cells following
Mtb
challenge or BCG vaccination in three different mouse strains. Eleven
Mtb
-antigens were recognised across TB-resistant and susceptible mice. Confirming previous human data, several
Mtb
-antigens induced cytokines other than IFN-γ. Pulmonary cells from susceptible C3HeB/FeJ mice produced less TNF-α, agreeing with the TB-susceptibility phenotype. In addition, responses to several antigens were induced by BCG in C3HeB/FeJ mice, offering potential for boosting. Thus, recognition of promising
Mtb
-antigens identified in humans validates across multiple mouse TB-infection models with widely differing TB-susceptibilities. This offers translational tools to evaluate IVE-TB-antigens as diagnostic and vaccine antigens.