Nature - USA (2020-01-02)

(Antfer) #1

Article


Extended Data Fig. 9 | Post-challenge immune responses to mycobacterial
antigens. 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 ref lects a
primary response to Mtb. By contrast, responses in the IV BCG group were
lower than in the IDlow 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
IDlow. 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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