Table 2.
Passive transfer studies with monoclonal antibodies showing protective effects against experimental mycobacterial infection
| mAb (isotype) | Target antigen (type) | Model | Organism/antigen challenge (route) | mAb administration (timing to infection) | Change in CFU | Biological effect | Quantitative effect | Reference |
|---|---|---|---|---|---|---|---|---|
| 9d8 (IgG3) | AM (capsular polysaccharide) | Mouse (BALB/c and C57BL/6) | Mtb (ae and i.t.) | i.t. (simultaneous/preincubated mAb with Mtb) | ↔ Lungs, spleen and liver | Prolonged survival and enhanced containment of Mtb within granuloma centers | 30%–60% of mAb-treated mice survived >75 d (33% for >220 d) vs. death in control mice within 30 d (p < 0.01) | Teitelbaum et al. 1998 |
| 4057 (IgG3) | HBHA (surface-exposed protein) | Mouse (BALB/c) | BCG (i.n.) | i.n. (simultaneous/preincubated mAb with BCG) | ↔ Lungs↓ Spleen | Reduction of disease dissemination | Reduced spleen colonization by ∼3 log(10) CFUs 3 wk postinfection in mAb-treated mice compared with controls (p value not stated) | Pethe et al. 2001 |
| TBA61 (IgA) | 16-kDa α-crystallin (intracellular and cell wall protein) | Mouse (BALB/c) | Mtb (ae and i.n.) | i.n. (3 h before and 3 or 6 d after) | ↓ Lungs | CFU reduction in early disease | Reduced lung colonization by ∼1 log(10) CFU 9 d postinfection in mAb-treated mice compared with controls (p < 0.01) | Williams et al. 2004 |
| SMITH14 (IgG1) | AM portion of LAM (cell wall glycolipid) | Mouse (BALB/c) | Mtb (i.v.) | i.v. (simultaneous/preincubated mAb with Mtb or 1 h prior) | ↓ Lungs↓ Liver↓ Spleen | CFU reduction and prolonged survival | Reduced lung, liver, and spleen colonization by ∼1–2 log(10) CFU 14 d postinfection in mAb-treated mice 1 h before infection compared with controls (p < 0.05 lungs and p < 0.01 liver and spleen) and survival of 7–8/10 (75%) mAb-treated mice versus 4/10 (40%) controls at 70 d (p < 0.01) | Hamasur et al. 2004 |
| MBS43 (IgG2b) | MPB83 (cell wall and CF protein) | Mouse (BALB/c) | Mycobacterium bovis (i.v.) | i.n. (simultaneous/pre-incubated mAb with M. bovis) | ↔ Lungs↔ Spleen↔ Liver | Reduced lung pathology and prolonged survival | Twice the estimated amount of normal lung tissue in mAb-treated mice compared with controls (p < 0.05) and 8/8 (100%) of mAb-treated mice survived >38 d (end of experiment) versus 0/8 (0%) of control mice (death within 30–34 d) (p < 0.005) | Chambers et al. 2004 |
| TBA61 (IgA) and TBA84 (IgA) | 16 kDa α-crystallin (intracellular and cell wall protein) and 38-kDa PstS-1 (CF protein) | Mouse (BALB/c) | Mtb (i.t.) | i.t. (mAb given 30 min before infection) | ↓ Lungs (only for TBA61) | Reduced lung pathology (only for TBA61) | Reduced lung colonization by ∼200 × 103 CFU 21 d postinfection in mAb TBA61-treated mice compared with controls and TBA84-treated mice (p < 0.05) and reduced peribronchial inflammation in TBA61-treated mice compared with controls 21 d post-infection (p < 0.05) | Lopez et al. 2009 |
| TBA61 (IgA) | 16-kDa α-crystallin (intracellular and cell wall protein) | Mouse (BALB/c, C57BL/6, C3H/HeJ) | Mtb (i.v.) | i.n. and i.v. given at 3, 5, or 7 wk as CIT with INF-γ, polyclonal Ab against IL-4, and mAbTBA61 in mice treated for 4 wk with INH/R | ↓ Lungs in CIT-treated mice | Prevention of TB relapse in mice treated with CIT together with ↑ granuloma formation and ↑ cyto- and chemokine levels | Reduced lung colonization by ∼3–4 log(10) CFU 8 wk postinfection in CIT-treated mice compared with controls; strongest protection when CIT given 5 wk postinfection (p = 0.001) | Buccheri et al. 2009 |
| 2E9 (IgA1) | 16-kDa α-crystallin (intracellular and cell wall protein) | Mouse (CD89tg) | Mtb (i.n.) | i.n. with and without INF-γ (2 h prior and 1 or 21 d post) | ↓ Lungs↓ Spleen | Reduced lung pathology | Reduced lung colonization by <1 log(10) CFU 4 wk postinfection in mAb plus INF-γ-treated mice compared with controls (p < 0.05) and significantly reduced lung granuloma formation in mAb-treated mice (<10%) compared with controls (∼45%; p < 0.001) | Balu et al. 2011 |
Data in table reproduced with permission from Achkar and Casadevall 2013.
mAb, monoclonal Ab; CFU, colony-forming units; INF-γ, interferon-γ; IL, interleukin; AM, arabinomannan; LAM, lipoarabinomannan; HBHA, heparin-binding hemaglutinin; Mtb, M. tuberculosis; CF, culture filtrate; CIT, combined immunotherapy; INH/R, isoniazid and rifampin; ae, aerosol; i.n., intranasal; i.v., intravenous; i.t., intratracheal.