TABLE 4

TB studies using cynomolgus macaquesa

Exptl designMajor findingsReference(s)
No. of CMM. tuberculosis strain (inoculation), dose(s) (CFU)
28Erdman (i.t.), 10–100,000Philippine CM provide an excellent model of chronic TB25
17Erdman (i.b.), 25Low-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 TB10
16Erdman (i.t.), 500CM vaccination with the 72f rBCG vaccine provides better protective efficacy than with BCG44b
44Erdman (i.t.), 500CM vaccination with the HSP65 plus IL-12/HVJ vaccine provides better protective efficacy than BCG44, 45b
15Erdman (i.t.), dose not reportedCM vaccination with Mtb72F/AS02A provides greater protective efficacy than BCG alone46b
24Erdman (i.b.), 1,000CM vaccination with mc26020 or mc26030 provides less protection than with BCG15b
25Erdman (i.b.), 25At 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 TB47
24Erdman (i.b.), 25Neutralization of TNF results in disseminated disease in acute and latent TB infection with normal granuloma structure in a CM model48
41Erdman (i.b.), 25Increased regulatory T cells in active TB occur in response to increased inflammation, not as a causal factor of disease progression49
15Erdman (i.b.), 25Reactivation of latent TB with SIV is associated with early T cell depletion and not virus load50
7Erdman (i.b.), 25M. tuberculosis-specific multifunctional T cells are better correlates of antigen load and disease status than of protection51c
5Erdman (i.b.), 200
33Erdman (i.t.), 25–500The multistage vaccine H56 boosts effects of BCG to protect CM against active TB and reactivation of latent TB52
14Erdman (i.b.), 25–200The CM model of M. tuberculosis infection mimics human TB, particularly in granuloma type and structure53
8Erdman (i.t.), 250M. tuberculosis may modulate protective immune responses via the use of indoleamine 2,3-dioxygenase (an immunosuppressant) found in nonlymphocytic regions of TB granulomas14b
9Erdman (i.b.), 25Experimental and epidemiologic estimates of the M. tuberculosis mutation rate are comparable54
27Erdman (i.b.), 500Early expansion/differentiation of Vγ2Vδ2 T effector cells during M. tuberculosis infection increases resistance to TB55
26Erdman (i.b.), 25–400TB 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 treatment56
12Erdman (i.b.), 1,000Compared 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 lungs58b
39Erdman (i.b.), 25Sterilization of TB granulomas occurs in both active and latent TB amid the differential killing of M. tuberculosis within a single host57
2SNP strains (i.b.), 34
8Erdman (i.b.), 240–500CM 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 lungs59b
  • a Abbreviations: 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.

  • b TB vaccine-related study.

  • c Animals were coinfected with M. tuberculosis and SIV.