Article
Extended Data Fig. 10 | Inf lammation and gross and histopathological
assessment after BCG vaccination. a, Serial FDG PET–CT scans at 2 and 4
weeks after BCG vaccination showed increased metabolism (surrogate for
inf lammation) localized to the lung LNs (green arrows), lung lobes and spleen
(yellow arrow) elicited by the IV but not by other routes (cohort 5a, b, n = 2
macaques). Warm colours indicate increased FDG retention; scale represents
standardized uptake values. NHP ID numbers are listed above each scan; ‘H’
denotes the heart. b, Spleen volume was calculated from CT scans at 2 and 4
weeks after BCG vaccination (n = 2 macaques). At these time points, animals
given IV BCG had approximately twofold larger spleens than those given ID
BCG, with AE/ID BCG NHPs also displaying modestly enlarged spleens.
c, Thoracic LNs were measured at necropsy, 4 weeks after BCG vaccination
(n = 2 macaques); LNs from IV BCG NHPs were enlarged compared to those from
IDlow NHPs. Kruskal–Wallis test was run; Dunn’s adjusted P values are reported
comparing each vaccine group to the IDlow group. d, e, H&E-stained sections of
thoracic LNs from vaccinated NHPs (n = 2 macaques), 4 weeks after BCG
vaccination. d, General structure with respect to cortical and medullary
architecture and appearance was normal in LNs from IDlow, IDhigh and AE/ID
vaccinated NHPs. The thoracic LNs from the IV-vaccinated macaques
demonstrated marked follicular lymphoid hyperplasia, with enlarged,
prominent, variably sized follicles, often with active, expanded germinal
centres. Original magnification, ×4. e, Small, non-necrotizing epithelioid
histiocytic aggregates (non-necrotizing granulomas, black arrows) were
abundantly disseminated within thoracic LNs from the IV BCG macaques. In the
AE/ID NHPs, a wide nodal distribution of such lesions was also seen, although
granuloma numbers and density were substantially less. The IDhigh NHPs had
only one observable granuloma in a single thoracic LN and in the IDlow NHPs, no
such structures were evident. Original magnification, ×10.