TABLE 3

TB studies using rhesus macaquesa

Exptl designMajor findingsReference(s)
No. of RMM. tuberculosis strainb (inoculation route), dose(s) (CFU)
8Erdman (i.b.), 10–150RM are a good model for latent TB, with use of low doses of H37Rv26
12H37Rv (i.b.), 30–6,000,000
4H37Rv (i.b.), 1,000High-resolution radiographic and fine immunologic studies provide definition of TB disease progression27
18Erdman (i.t.), 500Recombinant BCG (AFRO-1) induces strong antigen-specific T cell responses with TB vaccine vector (rAD35)28, 29c
24Erdman (i.t.), 1,000MVA.85 boosting of BCG and an attenuated, phoP-deficient TB vaccine show protective efficacy against TB30c
16Erdman K01 (aerosol), 40–65RM may be used as models of M. tuberculosis aerosol challenge; IFN-γ (ELISpot, ELISA) does not correlate with protection against TB; only MRI offers a reliable correlate31
NPNPEarly TB lesions have a highly proinflammatory environment, expressing IFN-γ, TNF-α, JAK, STAT, and C-C/C-X-C chemokines; in contrast, late TB lesions have a silenced inflammatory response32
12326 CDC1551 Himar 1 mutants (i.n.), 100,000Virulence mechanisms of M. tuberculosis include transport of lipid virulence factors, biosynthesis of cell wall arabinan and peptidoglycan, DNA repair, sterol metabolism, and lung cell entry33
9H37Rv (i.b.), 50–3,000Chinese RM are highly susceptible to M. tuberculosis infection and develop active TB regardless of the dose of strain H37Rv or Erdman used34, 35
24Erdman (i.b.), 25–500
16CDC1551 (i.n.), 50RM are an excellent model of TB/HIV coinfection and can be used to study TB latency and reactivation36
6Erdman K01 (i.b.), 500Stereological analysis quantitative data show a strong correlation between bacterial load and lung granulomas37
13CDC1551 (i.n.), 5,000The M. tuberculosis stress response factor sigH is required for M. tuberculosis growth and replication in mammalian lungs38
3Erdman (i.b./i.n.), 5–50Newborn macaques infected with aerosolized M. tuberculosis develop human-like immunologic responses and are a good model for pediatric TB/HIV40
32Erdman K01 (i.b.), 275RM aerosol vaccination with AERAS-402 elicits transient cellular immune responses in blood and robust, sustained immune responses in BAL fluid but does not protect against high-dose M. tuberculosis infection13c
17CDC1551 (aerosol), 100Clinical profiles vary considerably among RM infected with M. tuberculosis but can help identify predictive biomarkers for TB susceptibility along with gene expression profiles41
  • a All studies, except for those reported in references 28 to 30 and 33, used Indian rhesus macaques. Abbreviations: i.d., intradermal; i.n., intranasal; NP, not provided.

  • b The Erdman strain is most commonly used to study acute TB. It is a virulent subset of M. tuberculosis and exists in two forms, the laboratory isolate ATCC 35801 and the clinical isolate, K01; the Erdman ATCC 35801 strain was used in most studies, except those for which the K01 strain is indicated. H37RV is an attenuated laboratory strain of M. tuberculosis typically used to study latent TB infection. CDC1551 is a clinical isolate of M. tuberculosis and exhibits a similar degree of virulence as the Erdman strain.

  • c TB vaccine-related study.