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. 2020 Jan 1;577(7788):95–102. doi: 10.1038/s41586-019-1817-8

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 9 — a, PBMC response to ESAT-6 or CFP-10 peptides (antigens present in Mtb but not BCG) as determined by IFNγ ELISpot throughout Mtb infection. Each line is one NHP over time (n = 8–10 macaques; n = 4 unvaccinated); sterile animals are represented by a triangle, and non-sterile, protected animals (with 1 ≤ CFUs ≤ 50) denoted by squares. After infection, most animals in the AE or ID vaccine groups developed ESAT-6 or CFP10 ELISpot responses, which reflects a primary response to Mtb. By contrast, responses in the IV BCG group were lower than in the ID_low group at every time point after infection for ESAT-6 (4 weeks, P = 0.001; 6 weeks, P = 0.045; 8 weeks, P = 0.025; 12 weeks, P = 0.006) and CFP-10 (4 weeks, P < 0.0001; 6 weeks, P = 0.035; 8 weeks, P = 0.001; 12 weeks, P = 0.004). Kruskal–Wallis test was run at each time point with Dunn’s adjusted P values reported accounting for comparisons of all groups against ID_low. b, c, The frequency of memory CD4 (b) and CD8 (c) T cells in PBMCs from BCG-immunized NHPs (n = 8–10) producing any combination of IFNγ, IL-2, TNF or IL-17 in response to stimulation with either PPD (antigen present in BCG and Mtb; top row) or pooled ESAT-6 and CFP-10 peptides (antigens present in Mtb only; bottom row) were measured at the time of challenge (0), and at 4, 8 and 12 weeks after Mtb challenge. Measurements from four unvaccinated, infected NHPs are included as controls (Unvax, black). Grey lines represent the responses of individual animals and bolded, coloured lines are the mean responses for each vaccine group. d, Antibody responses post-challenge. Mtb WCL-specific IgG, IgA and IgM antibody titres were measured in the plasma of unvaccinated (n = 4) and vaccinated (n = 8–10) NHPs at the time of challenge (0), and at 4 and 12 weeks after challenge. In b–d, Wilcoxon signed-rank unadjusted P values compare cytokine frequencies or antibody titres at week 12 after Mtb (or necropsy) to the time of challenge (week 0) within each vaccine group.

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