TABLE 4.

TB studies using cynomolgus macaques^a

Exptl design		Major findings	Reference(s)
No. of CM	M. tuberculosis strain (inoculation), dose(s) (CFU)
28	Erdman (i.t.), 10–100,000	Philippine CM provide an excellent model of chronic TB	25
17	Erdman (i.b.), 25	Low-dose infection of CM represents the full spectrum of human M. tuberculosis infection and provides a model to study latent as well as active-chronic and rapidly progressive TB	10
16	Erdman (i.t.), 500	CM vaccination with the 72f rBCG vaccine provides better protective efficacy than with BCG	44b
44	Erdman (i.t.), 500	CM vaccination with the HSP65 plus IL-12/HVJ vaccine provides better protective efficacy than BCG	44, 45b
15	Erdman (i.t.), dose not reported	CM vaccination with Mtb72F/AS02A provides greater protective efficacy than BCG alone	46b
24	Erdman (i.b.), 1,000	CM vaccination with mc26020 or mc26030 provides less protection than with BCG	15b
25	Erdman (i.b.), 25	At necropsy, CM with active TB have more lung T cells and more IFN-γ from PBMC, BAL fluid, and mediastinal lymph nodes than CM with latent TB	47
24	Erdman (i.b.), 25	Neutralization of TNF results in disseminated disease in acute and latent TB infection with normal granuloma structure in a CM model	48
41	Erdman (i.b.), 25	Increased regulatory T cells in active TB occur in response to increased inflammation, not as a causal factor of disease progression	49
15	Erdman (i.b.), 25	Reactivation of latent TB with SIV is associated with early T cell depletion and not virus load	50
7	Erdman (i.b.), 25	M. tuberculosis-specific multifunctional T cells are better correlates of antigen load and disease status than of protection	51c
5	Erdman (i.b.), 200
33	Erdman (i.t.), 25–500	The multistage vaccine H56 boosts effects of BCG to protect CM against active TB and reactivation of latent TB	52
14	Erdman (i.b.), 25–200	The CM model of M. tuberculosis infection mimics human TB, particularly in granuloma type and structure	53
8	Erdman (i.t.), 250	M. tuberculosis may modulate protective immune responses via the use of indoleamine 2,3-dioxygenase (an immunosuppressant) found in nonlymphocytic regions of TB granulomas	14b
9	Erdman (i.b.), 25	Experimental and epidemiologic estimates of the M. tuberculosis mutation rate are comparable	54
27	Erdman (i.b.), 500	Early expansion/differentiation of Vγ2Vδ2 T effector cells during M. tuberculosis infection increases resistance to TB	55
26	Erdman (i.b.), 25–400	TB granulomas evolve and resolve independently within a single host; individual lesions respond differently to different drugs; overall PET and CT signals can predict successful TB drug treatment	56
12	Erdman (i.b.), 1,000	Compared to nonvaccinated CM, BCG-vaccinated CM exhibit higher expression levels of TNF-α, IL-10, IL-1b, TLR4, IL-17, IL-6, IL-12, and iNOS in lungs	58b
39	Erdman (i.b.), 25	Sterilization of TB granulomas occurs in both active and latent TB amid the differential killing of M. tuberculosis within a single host	57
2	SNP strains (i.b.), 34
8	Erdman (i.b.), 240–500	CM vaccination with BCG transiently increases levels of macrophages and lymphocytes in blood, with later recruitment in the lungs; however, M. tuberculosis continues to replicate in lungs	59b

^aAbbreviations: SNP strains, strains with a single-nucleotide polymorphism mutation; rBCG, recombinant BCG; BAL, bronchoalveolar lavage; PBMC, peripheral blood mononuclear cells; iNOS, inducible nitric oxygen synthase.

^bTB vaccine-related study.

^cAnimals were coinfected with M. tuberculosis and SIV.