TABLE 3.

TB studies using rhesus macaques^a

Exptl design		Major findings	Reference(s)
No. of RM	M. tuberculosis strainb (inoculation route), dose(s) (CFU)
8	Erdman (i.b.), 10–150	RM are a good model for latent TB, with use of low doses of H37Rv	26
12	H37Rv (i.b.), 30–6,000,000
4	H37Rv (i.b.), 1,000	High-resolution radiographic and fine immunologic studies provide definition of TB disease progression	27
18	Erdman (i.t.), 500	Recombinant BCG (AFRO-1) induces strong antigen-specific T cell responses with TB vaccine vector (rAD35)	28, 29c
24	Erdman (i.t.), 1,000	MVA.85 boosting of BCG and an attenuated, phoP-deficient TB vaccine show protective efficacy against TB	30c
16	Erdman K01 (aerosol), 40–65	RM 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 correlate	31
NP	NP	Early 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 response	32
12	326 CDC1551 Himar 1 mutants (i.n.), 100,000	Virulence mechanisms of M. tuberculosis include transport of lipid virulence factors, biosynthesis of cell wall arabinan and peptidoglycan, DNA repair, sterol metabolism, and lung cell entry	33
9	H37Rv (i.b.), 50–3,000	Chinese RM are highly susceptible to M. tuberculosis infection and develop active TB regardless of the dose of strain H37Rv or Erdman used	34, 35
24	Erdman (i.b.), 25–500
16	CDC1551 (i.n.), 50	RM are an excellent model of TB/HIV coinfection and can be used to study TB latency and reactivation	36
6	Erdman K01 (i.b.), 500	Stereological analysis quantitative data show a strong correlation between bacterial load and lung granulomas	37
13	CDC1551 (i.n.), 5,000	The M. tuberculosis stress response factor sigH is required for M. tuberculosis growth and replication in mammalian lungs	38
3	Erdman (i.b./i.n.), 5–50	Newborn macaques infected with aerosolized M. tuberculosis develop human-like immunologic responses and are a good model for pediatric TB/HIV	40
32	Erdman K01 (i.b.), 275	RM 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 infection	13c
17	CDC1551 (aerosol), 100	Clinical profiles vary considerably among RM infected with M. tuberculosis but can help identify predictive biomarkers for TB susceptibility along with gene expression profiles	41

^aAll 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.

^bThe 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.

^cTB vaccine-related study.