Re-evaluating the Role of Antibodies in Tuberculosis
by Pia Steigler, PhD
Alene, K. A., Wangdi, K., Colquhoun, S., Chani, K., Islam, T., Rahevar, K., Morishita, F., Byrne, A.,
Clark, J., & Viney, K. (2021). Tuberculosis related disability: a systematic review and meta-analysis.
BMC Medicine, 19(1).
Awoniyi, D. O., Baumann, R., Chegou, N. N., Kriel, B., Jacobs, R., Kidd, M., Loxton, A. G.,
Kaempfer, S., Singh, M., & Walzl, G. (2017). Detection of a combination of serum IgG and IgA
antibodies against selected mycobacterial targets provides promising diagnostic signatures for ac-
tive tuberculosis. Oncotarget, 8, 3752537537.
Baumann, R., Kaempfer, S., Chegou, N. N., Oehlmann, W., Loxton, A. G., Kaufmann, S. H. E., van
Helden, P. D., Black, G. F., Singh, M., & Walzl, G. (2014). Serologic diagnosis of tuberculosis by
combining Ig classes against selected mycobacterial targets. The Journal of Infection, 69(6), 581589.
Bekker, L. G., Dintwe, O., Fiore-Gartland, A., Middelkoop, K., Hutter, J., Williams, A., Randhawa, A.
K., Ruhwald, M., Kromann, I., Andersen, P. L., DiazGranados, C. A., Rutkowski, K. T., Tait, D., Miner,
M. D., Andersen-Nissen, E., de Rosa, S. C., Seaton, K. E., Tomaras, G. D., McElrath, M. J., Kublin,
J. G. (2020). A phase 1b randomized study of the safety and immunological responses to vaccination
with H4:IC31, H56:IC31, and BCG revaccination in Mycobacterium tuberculosis-uninfected adolescents
in Cape Town, South Africa. EClinicalMedicine, 21.
Brown, S., Leavy, J. E., & Jancey, J. (2021). Implementation of GeneXpert for TB testing in low- and
middle-income countries: a systematic review. Global Health: Science and Practice, 9(3), 698710.
Bulterys, M. A., Wagner, B., Regard-Jacot, M., Suresh, A., Pollock, N. R., Moreau, E., Denkinger, C.
M., Drain, P. K., & Broger, T. (2019). Point-of-care urine LAM tests for tuberculosis diagnosis: a status
update. Journal of Clinical Medicine 2020, Vol. 9, Page 111, 9(1), 111.
Carrère-Kremer, S., Kolia-Diafouka, P., Pisoni, A., Bolloré, K., Peries, M., Godreuil, S., Bourdin, A.,
van de Perre, P., & Tuaillon, E. (2022). QuantiFERON-TB Gold Plus assay in patients with latent vs.
active tuberculosis in a low incidence setting: level of IFN-γ, CD4/CD8 responses, and release of IL-
2, IP-10, and MIG. Frontiers in Microbiology, 13.
Casadevall, A., & Scharff, M. D. (1995). Return to the past: the case for antibody-based therapies in
infec tious diseases. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society
of America, 21(1), 150161. 10.1093/clinids/21.1.150
Chen, T., Blanc, C., Eder, A. Z., Prados-Rosales, R., Souza, A. C. O., Kim, R. S., Glatman-Freedman,
A., Joe, M., Bai, Y., Lowary, T. L., Tanner, R., Brennan, M. J., Fletcher, H. A., McShane, H., Casade-
vall, A., & Achkar, J. M. (2016). Association of human antibodies to arabinomannan with en-
hanced mycobacterial opsonophagocytosis and intracellular growth reduction. Journal of Infectious
Diseases, 214(2), 300310.
Desikan, P., Tiwari, K., Panwalkar, N., Khaliq, S., Chourey, M., Varathe, R., Mirza, S. B., Sharma, A.,
Anand, S., & Pandey, M. (2017). Public health relevance of non-tuberculous mycobacteria among
AFB posi tive sputa. Germs, 7(1), 10.
Dijkman, K., Sombroek, C. C., Vervenne, R. A. W., Hofman, S. O., Boot, C., Remarque, E. J., Kocken,
C. H. M., Ottenhoff, T. H. M., Kondova, I., Khayum, M. A., Haanstra, K. G., Vierboom, M. P. M., &
Verreck, F. A. W. (2019). Prevention of tuberculosis infection and disease by local BCG in repeat-
edly exposed rhesus macaques. Nature Medicine, 25(2), 255262.
Fletcher, H. A., Snowden, M. A., Landry, B., Rida, W., Satti, I., Harris, S. A., Matsumiya, M., Tanner,
R., Oshea, M. K., Dheenadhayalan, V., Bogardus, L., Stockdale, L., Marsay, L., Chomka, A.,
Harrington-Kandt, R., Manjaly-Thomas, Z. R., Naranbhai, V., Stylianou, E., Darboe, F., … McShane,
H. (2016). T-cell activation is an immune correlate of risk in BCG-vaccinated infants. Nature
Communications, 7(11290), 110.
Glatman-freedman, A., & Schweinitz, D. (1998). Serum Therapy for Tuberculosis Revisited:
Reappraisal of the Role of Antibody-Mediated Immunity against Mycobacterium tuberculosis. Clinical
Microbiology Reviews, 11(3), 514532. 10.1128/CMR.11.3.514
Hamasur, B., Haile, M., Pawlowski, A., Schröder, U., Källenius, G., & Svenson, S. B. (2004). A my
cobacterial lipoarabinomannan specific monoclonal antibody and its F(ab′)2 fragment prolong
survival of mice infected with Mycobacterium tuberculosis. Clinical and Experimental Immunology,
138(1), 3038.
Irvine, E. B., O’Neil, A., Darrah, P. A., Shin, S., Choudhary, A., Li, W., Honnen, W., Mehra, S., Kaushal,
D., Gideon, H. P., Flynn, J. A. L., Roederer, M., Seder, R. A., Pinter, A., Fortune, S., & Alter, G. (2021).
Robust IgM responses following intravenous vaccination with Bacille Calmette–Guérin associate
with prevention of Mycobacterium tuberculosis infection in macaques. Nature Immunology 2021 22:12,
22(12), 15151523.
Jasenosky, L. D., Scriba, T. J., Hanekom, W. A., & Goldfeld, A. E. (2015). T cells and adaptive immun-
ity to Mybacterium tuberculosis in humans. Immunological Reviews, 264(1), 7487.
Khaliq, A., Ravindran, R., Hussainy, S. F., Krishnan, V. v., Ambreen, A., Yusuf, N. W., Irum, S.,
Rashid, A., Jamil, M., Zaffar, F., Chaudhry, M. N., Gupta, P. K., Akhtar, M. W., & Khan, I. H.
(2017). Field evaluation of a blood based test for active tuberculosis in endemic settings. PloS One,
Kumar, S. K., Singh, P., & Sinha, S. (2015). Naturally produced opsonizing antibodies restrict the
survival of Mycobacterium tuberculosis in human macrophages by augmenting phagosome maturtion.
Open Biology, 5(12), 150171.
Kumarasamy, N., Poongulali, S., Beulah, F. E., Akite, E. J., Ayuk, L. N., Bollaerts, A., Demoitié, M. A.,
Jongert, E., Ofori-Anyinam, O., & van der Meeren, O. (2018). Long-term safety and immunogenicity
of the M72/AS01E candidate tuberculosis vaccine in HIV-positive and -negative Indian adults:
Reults from a phase II randomized controlled trial. Medicine, 97(45).
Li, H., Wang, X., Wang, B., Fu, L., Liu, G., Lu, Y., Cao, M., Huang, H., & Javid, B. (2017). Latently
and uninfected healthcare workers exposed to TB make protective antibodies against Mycobac
terium tuberculosis. Proceedings of the National Academy of Sciences, 114(19), 50235028.
Lu, L. L., Chung, A. W., Rosebrock, T. R., Ghebremichael, M., Yu, W. H., Grace, P. S., Schoen, M. K.,
Tafesse, F., Martin, C., Leung, V., Mahan, A. E., Sips, M., Kumar, M. P., Tedesco, J., Robinson, H.,
Tkachenko, E., Draghi, M., Freedberg, K. J., Streeck, H., … Alter, G. (2016). A functional role for
antibodies in tuberculosis. Cell, 167(2), 433443.
McLean, M. R., Lu, L. L., Kent, S. J., & Chung, A. W. (2019). An inflammatory story: Antibodies in
tuberculosis comorbidities. In Frontiers in Immunology (Vol. 10, Issue 2846). Frontiers Media S.A.
Menzies, N. A., Swartwood, N., Testa, C., Malyuta, Y., Hill, A. N., Marks, S. M., Cohen, T., & Sa
lomon, J. A. (2021). Time Since Infection and Risks of Future Disease for Individuals with Mycobacrium
tuberculosis Infection in the United States. Epidemiology (Cambridge, Mass.), 32(1), 70.
Murphy, K. M. K., T. P., W. M. and J. C. (2012). Janeway’s Immunobiology: Vol. 8th Edition.
Penn-Nicholson, A., Geldenhuys, H., Burny, W., Most, R. van der, Day, C. L., Jongert, E., Moris, P.,
Hatherill, M., Ofori-Anyinam, O., Hanekom, W., Tuberculosis, A., Initiative, V., Health, C., Town,
C., & Africa, S. (2015). Safety and immunogenicity of candidate vaccine M72/AS01E in adolescents in a TB
endemic setting. 33(32), 40254034.
Petruccioli, E., Vanini, V., Chiacchio, T., Cuzzi, G., Cirillo, D. M., Palmieri, F., Ippolito, G., & Goletti,
D. (2017). Analytical evaluation of QuantiFERON- Plus and QuantiFERON- Gold In-tube assays in
subjects with or without tuberculosis. Tuberculosis, 106(S5), 3843.
Plotkin, S. A. (2010). Correlates of protection induced by vaccination. Clinical and Vaccine Immunology,
17(7), 10551065.
Riley, R. L., Mills, C. C., Nyka, W., Weinstock, N., Storey, P. B., Sultan, L. U., Riley, M. C., & Wells,
W. F. (1995). Aerial dissemination of pulmonary tuberculosis. A two-year study of contagion in a
tuberculosis ward. 1959. American Journal of Epidemiology, 142(1), 314.
Sabur, N. F., Esmail, A., Brar, M. S., & Dheda, K. (2017). Diagnosing tuberculosis in hospitalized
HIV-infected individuals who cannot produce sputum: Is urine lipoarabinomannan testing the
answer? BMC Infectious Diseases, 17(1), 16. 79-017-2914-7
Steigler, P., Verrall, A. J., & Kirman, J. R. (2019). Beyond memory T cells: mechanisms of protective
immunity to tuberculosis infection. Immunology and Cell Biology, 97(7), 647655.
Steingart, K. R., Flores, L. L., Dendukuri, N., Schiller, I., Laal, S., Ramsay, A., Hopewell, P. C., & Pai,
M. (2011). Commercial serological tests for the diagnosis of active pulmonary and extrapulmonary
tuberculosis: An updated systematic review and meta-analysis. PLoS Medicine, 8(8), e1001062.
Tait, D. R., Hatherill, M., der Meeren, O. van, Ginsberg, A. M., van Brakel, E., Salaun, B., Scriba, T.
J., Akite, E. J., Ayles, H. M., Bollaerts, A., Demoitié, M. A., Diacon, A., Evans, T. G., Gillard, P.,
Hellström, E., Innes, J. C., Lempicki, M., Malahleha, M., Martinson, N., et al. (2019). Final
analysis of a trial of M72/AS01
vaccine to prevent tuberculosis. New England Journal of Medicine,
381(25), 24292439.
Trunz, B. B., Fine, P., & Dye, C. (2006). Effect of BCG vaccination on childhood tuberculous menin
gitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness.
Lancet, 367(9517), 11731180.
Venturini, E., Turkova, A., Chiappini, E., Galli, L., de Martino, M., & Thorne, C. (2014). Tuberculosis
and HIV co-infection in children. BMC Infectious Diseases, 14 (Suppl 1).
Vynnycky, E., & Fine, P. E. M. (1997). The natural history of tuberculosis: the implications of age-de
pendent risks of disease and the role of reinfection. Epidemiology and Infection, 119(2), 183201.
Watson, A., Li, H., Ma, B., Weiss, R., Bendayan, D., Abramovitz, L., Ben-Shalom, N., Mor, M., Pinko,
E., Bar Oz, M., Wang, Z., Du, F., Lu, Y., Rybniker, J., Dahan, R., Huang, H., Barkan, D., Xiang, Y.,
Javid, B., & Freund, N. T. (2021). Human antibodies targeting a Mycobacterium transporter protein
mediate protection against tuberculosis. Nature Communications, 12, 602 (2021)
Wilkie, M., Satti, I., Minhinnick, A., Harris, S., Riste, M., Ramon, R. L., Sheehan, S., Thomas, Z. R.
M., Wright, D., Stockdale, L., Hamidi, A., O’Shea, M. K., Dwivedi, K., Behrens, H. M., Davenne,
T., Morton, J., Vermaak, S., Lawrie, A., Moss, P., & McShane, H. (2020). A phase I trial evaluating
the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1
85Aprime MVA85A boost in healthy UK adults. Vaccine, 38(4), 779789.
World Health Organization. (2011). Commercial serodiagnostic tests for diagnosis of tuberculosis:
Policy statement. WHO Press.
World Health Organization. (2021). Module 3: Diagnosis WHO consolidated guidelines on
Tuberculosis. Rapid diagnostics for tuberculosis detection. WHO Press, Geneva.
World Health Organization. (2022). Global Tuberculosis Report 2022. WHO Press, Geneva.
Zimmermann, N., Thormann, V., Hu, B., Köhler, A., Imai-matsushima, A., Locht, C., Arnett, E., Schle-
singer, L. S., Zoller, T., Schürmann, M., Kaufmann, S. H. E., & Wardemann, H. (2016). Human istype-
dependent inhibitory antibody responses against Mycobacterium tuberculosis. EMBO Mol. Med., 8(11),