Attenuated Mycobacterium tuberculosis vaccine protection in a low-dose murine challenge model.

Autor:	Vidal SJ; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.; Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Sellers D; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Yu J; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Wakabayashi S; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Sixsmith J; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Aid M; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Barrett J; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Stevens SF; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Liu X; Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA., Li W; Department of Public Health, University of Massachusetts Lowell, Lowell, MA, USA., Plumlee CR; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA., Urdahl KB; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA.; Department of Pediatrics, University of Washington, Seattle, WA, USA.; Department of Immunology, University of Washington, Seattle, WA, USA., Martinot AJ; Department of Infectious Diseases and Global Health, Tufts University Cummings School of Veterinary Medicine, North Grafton, MA, USA., Barouch DH; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2023 May 28; Vol. 26 (6), pp. 106963. Date of Electronic Publication: 2023 May 28 (Print Publication: 2023).
DOI:	10.1016/j.isci.2023.106963
Abstrakt:	Bacillus Calmette-Guérin (BCG) remains the only approved tuberculosis (TB) vaccine despite limited efficacy. Preclinical studies of next-generation TB vaccines typically use a murine aerosol model with a supraphysiologic challenge dose. Here, we show that the protective efficacy of a live attenuated Mycobacterium tuberculosis (Mtb) vaccine ΔLprG markedly exceeds that of BCG in a low-dose murine aerosol challenge model. BCG reduced bacterial loads but did not prevent establishment or dissemination of infection in this model. In contrast, ΔLprG prevented detectable infection in 61% of mice and resulted in anatomic containment of 100% breakthrough infections to a single lung. Protection was partially abrogated in a repeated low-dose challenge model, which showed serum IL-17A, IL-6, CXCL2, CCL2, IFN-γ, and CXCL1 as correlates of protection. These data demonstrate that ΔLprG provides increased protection compared to BCG, including reduced detectable infection and anatomic containment, in a low-dose murine challenge model. Competing Interests: A.J.M. and D.H.B. are co-inventors on a provisional vaccine patent PCT/US2020/059152 (Mycobacterial compositions and biomarkers for use in treatment and monitoring of therapeutic responsiveness). (© 2023 The Authors.)
Databáze:	MEDLINE
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