Immunity Against Mycobacterium avium Induced by DAR-901 and BCG.
| Title: | Immunity Against Mycobacterium avium Induced by DAR-901 and BCG. |
|---|---|
| Authors: | Abate G; Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine, Saint Louis University, St. Louis, MO 63104, USA.; Meza KA; Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine, Saint Louis University, St. Louis, MO 63104, USA.; Colbert CG; Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine, Saint Louis University, St. Louis, MO 63104, USA.; Ramos-Espinosa O; Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine, Saint Louis University, St. Louis, MO 63104, USA.; Phillips NJ; Department of Pathology, Saint Louis University, St. Louis, MO 63104, USA.; Eickhoff CS; Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine, Saint Louis University, St. Louis, MO 63104, USA. |
| Source: | Vaccines [Vaccines (Basel)] 2025 Jun 07; Vol. 13 (6). Date of Electronic Publication: 2025 Jun 07. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101629355 Publication Model: Electronic Cited Medium: Print ISSN: 2076-393X (Print) Linking ISSN: 2076393X NLM ISO Abbreviation: Vaccines (Basel) Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI AG |
| Abstract: | Background: The prevalence of pulmonary nontuberculous mycobacteria (NTM) is increasing in Europe and North America. Most pulmonary NTM cases are caused by Mycobacterium avium complex (MAC). The treatment of pulmonary MAC is suboptimal with failure rates ranging from 30% to 40% and there is a need to develop new vaccines. Methods: We tested the ability of two whole-cell vaccines, DAR-901 (heat-killed M. obuense) and BCG (live-attenuated M. bovis), to induce MAC cross-reactive immunity by first immunizing BALB/c mice and then performing IFN-γ ELISPOT assays after overnight stimulation of splenocytes with live MAC. To study the ability of these vaccines to protect against MAC infection, BALB/c mice were vaccinated with DAR-901 (intradermal) or BCG (subcutaneous or intranasal) and challenged with aerosolized MAC 4 weeks later. A group of mice vaccinated with BCG were also treated with clarithromycin via gavage. Lung colony-forming units (CFU) in immunized mice and unvaccinated controls were quantified 4 weeks after infection. Histopathology was used to quantify lung inflammation and flow cytometry was used to study lung immunity in BCG-vaccinated and unvaccinated mice following MAC infection. To increase the safety profile of mucosal BCG vaccination, we studied BCG with a "kill switch" (tetR BCG) in scnn1b-transgenic mice (i.e., mice prone to cystic fibrosis-type lung diseases). Results: Our results showed that (i) DAR-901 induced cross-reactive immunity to MAC to a similar level as BCG, (ii) DAR-901 and BCG protected against aerosol MAC challenge, (iii) mucosal BCG vaccination, compared to systemic BCG and DAR-901 vaccinations, provided the best protection against MAC challenge, (iv) BCG vaccination did not interfere with anti-MAC activities of clarithromycin, (v) BCG-vaccinated mice had increased inflammation and increased frequencies of activated CD4 and CD8 T cells following MAC infection, and (vi) doxycycline treatment of tetR BCG-vaccinated mice decreased lung BCG CFU without affecting MAC immunity. Conclusions: Both DAR-901 and BCG vaccinations induce MAC cross-reactive immunity and protect against aerosolized MAC challenges. Mucosal BCG vaccination provides the best protection and TetR BCG could enhance the safety of mucosal BCG vaccination. |
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| Contributed Indexing: | Keywords: BALB/c; BCG; DAR-901; M. avium; immunity |
| Entry Date(s): | Date Created: 20250627 Latest Revision: 20250630 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12197784 |
| DOI: | 10.3390/vaccines13060619 |
| PMID: | 40573950 |
| Database: | MEDLINE |
Journal Article