000099131 001__ 99131 000099131 005__ 20230519145448.0 000099131 0247_ $$2doi$$a10.1038/s41541-020-00262-8 000099131 0248_ $$2sideral$$a122582 000099131 037__ $$aART-2021-122582 000099131 041__ $$aeng 000099131 100__ $$aWhite, A.D. 000099131 245__ $$aMTBVAC vaccination protects rhesus macaques against aerosol challenge with M. tuberculosis and induces immune signatures analogous to those observed in clinical studies 000099131 260__ $$c2021 000099131 5060_ $$aAccess copy available to the general public$$fUnrestricted 000099131 5203_ $$aA single intradermal vaccination with MTBVAC given to adult rhesus macaques was well tolerated and conferred a significant improvement in outcome following aerosol exposure to M. tuberculosis compared to that provided by a single BCG vaccination. Vaccination with MTBVAC resulted in a significant reduction in M. tuberculosis infection-induced disease pathology measured using in vivo medical imaging, in gross pathology lesion counts and pathology scores recorded at necropsy, the frequency and severity of pulmonary granulomas and the frequency of recovery of viable M. tuberculosis from extrapulmonary tissues following challenge. The immune profiles induced following immunisation with MTBVAC reflect those identified in human clinical trials of MTBVAC. Evaluation of MTBVAC- and TB peptide-pool-specific T-cell cytokine production revealed a predominantly Th1 response from poly- (IFN-¿+TNF-a+IL2+) and multi-(IFN-¿+TNF-a+) functional CD4 T cells, while only low levels of Th22, Th17 and cytokine-producing CD8 T-cell populations were detected together with low-level, but significant, increases in CFP10-specific IFN-¿ secreting cells. In this report, we describe concordance between immune profiles measured in clinical trials and a macaque pre-clinical study demonstrating significantly improved outcome after M. tuberculosis challenge as evidence to support the continued development of MTBVAC as an effective prophylactic vaccine for TB vaccination campaigns. 000099131 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000099131 590__ $$a9.399$$b2021 000099131 592__ $$a2.953$$b2021 000099131 594__ $$a9.4$$b2021 000099131 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b21 / 140 = 0.15$$c2021$$dQ1$$eT1 000099131 593__ $$aImmunology$$c2021$$dQ1 000099131 591__ $$aIMMUNOLOGY$$b32 / 163 = 0.196$$c2021$$dQ1$$eT1 000099131 593__ $$aPharmacology (medical)$$c2021$$dQ1 000099131 593__ $$aInfectious Diseases$$c2021$$dQ1 000099131 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000099131 700__ $$aSibley, L. 000099131 700__ $$aSarfas, C. 000099131 700__ $$aMorrison, A. 000099131 700__ $$aGullick, J. 000099131 700__ $$aClark, S. 000099131 700__ $$aGleeson, F. 000099131 700__ $$aMcIntyre, A. 000099131 700__ $$aArlehamn, C.L. 000099131 700__ $$aSette, A. 000099131 700__ $$aSalguero, F.J. 000099131 700__ $$aRayner, E. 000099131 700__ $$aRodriguez, E. 000099131 700__ $$aPuentes, E. 000099131 700__ $$aLaddy, D. 000099131 700__ $$aWilliams, A. 000099131 700__ $$aDennis, M. 000099131 700__ $$0(orcid)0000-0003-2993-5478$$aMartin, C.$$uUniversidad de Zaragoza 000099131 700__ $$aSharpe, S. 000099131 7102_ $$11011$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Microbiología 000099131 773__ $$g6, 1 (2021), 4 [10 pp]$$pnpj Vaccines$$tnpj Vaccines$$x2059-0105 000099131 8564_ $$s767250$$uhttps://zaguan.unizar.es/record/99131/files/texto_completo.pdf$$yVersión publicada 000099131 8564_ $$s3338114$$uhttps://zaguan.unizar.es/record/99131/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000099131 909CO $$ooai:zaguan.unizar.es:99131$$particulos$$pdriver 000099131 951__ $$a2023-05-18-14:40:11 000099131 980__ $$aARTICLE