Repeated inoculations of Mycobacterium bovis Bacille Calmette-Guérin (BCG) are needed to induce a strong humoral immune response against antigens expressed by the bacteria — Oak Academic Publishing
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Repeated inoculations of Mycobacterium bovis Bacille Calmette-Guérin (BCG) are needed to induce a strong humoral immune response against antigens expressed by the bacteria
Laboratory of Biology of Recognition, Universidade Estadual do Norte Fluminense, Campos, Rio de Janeiro, Brazil
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Laboratory of Biology of Recognition, Universidade Estadual do Norte Fluminense, Campos, Rio de Janeiro, Brazil
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Laboratory of Immunochemistry, Institute Butantan, São Paulo, Brazil
1 Laboratory of Biology of Recognition, Universidade Estadual do Norte Fluminense, Campos, Rio de Janeiro, Brazil
2 Laboratory of Biology of Recognition, Universidade Estadual do Norte Fluminense, Campos, Rio de Janeiro, Brazil
3 Laboratory of Immunochemistry, Institute Butantan, São Paulo, Brazil
The cellular immune response elicited by My cobacterium bovis Bacille Calmette-Guérin (BCG) has been carefully investigated, but the humoral immune response has been partially neglected. BALB/c mice were immunized with BCG strain used to immunize humans. Anti-BCG antibodies, as assayed by ELISA, began to appear in the sera after the third week of immunization and plateaued three weeks after the 8 th immunization. The total immunoglobulins (Igs) were purified by caprylic acid method from pooled serum collected after the 8 th immunization. Anti-BCG antigen antibodies were detected in the total Igs preparation as well as in IgG, IgM, IgA, IgG 1 , IgG 2a , and IgG 2b , but not in the IgG 3 . Distinct BCG proteins were recognized the IgGs in Western blot analysis. Opsonization of BCG bacilli by the purified Igs potentiated internalization of the bacteria by murine Raw 264.7 macrophages. The intracellular BCG elimination coincided with the induction of NO production, which was more pronounced in cells infected with opsonized BCG compared to those infected with the non-opsonized bacteria. Coincidently, the production of NO was also higher in macrophages infected with opsonized BCG (maximal NO production at 48 h of incubation). The obtained results demonstrate that repeated inoculations of BCG effectively activate the humoral immune response, justifying the use of BCG as a live recombinant vaccine vector to insert genes encoding virulence factors controlled by antibodies.
Calmette, A. (1927) La vaccinacion preventive contre la tuberculose. Masson et Cie, Paris.
Colditz, G.A., Brewer, T.F., Berkey, C.S., Wilson, M.E., Burdick, E., Fineberg, H.V. and Mosteller, F. (1994) Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA, 271, 698- 702. doi:10.1001/jama.1994.03510330076038
Fine, P.E., Carneiro, I.A., Milstien, J.B. and Clemens, C.J. (1968) Issues related to the use of BCG in immunization programs: A discussion document. WHO, Geneva, 3-45.
Wilson, M.E., Fineberg, H.V. and Colditz, G.A. (1995) Geographic latitude and the efficacy of bacillus Calmette- Guerin vaccine. Clinical Infectious Diseases, 20, 982-991. doi:10.1093/clinids/20.4.982
Black, G.F., Weir, R.E., Floyd, S., Bliss, L., Warndorff, D.K., Crampin, A.C., Ngwira, B., Sichali, L., Nazareth, B., Blackwell, J.M., Branson, K., Chaguluka, S.D., Donovan, L., Jarman, E., King, E., Fine, P.E. and Dockrell, H.M. (2002) BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: Two randomised controlled studies. Lancet, 359, 1393-1401. doi:10.1016/S0140-6736(02)08353-8
Clemens, J.D., Chuong, J.J. and Feinstein, A.R. (1983) The BCG controversy. A methodological and statistical reappraisal. JAMA, 249, 2362-2369. doi:10.1001/jama.1983.03330410048027
Colditz, G.A., Berkey, C.S., Mosteller, F., Brewer, T.F., Wilson, M.E., Burdick, E. and Fineberg, H.V. (1995) The efficacy of bacillus Calmette-Guerin vaccination of newborns and infants in the prevention of tuberculosis: Meta-analyses of the published literature. Pediatrics, 96, 29-35.
Roach, T.I., Barton, C.H., Chatterjee, D. and Blackwell, J.M. (1993) Macrophage activation: Lipoarabinomannan from avirulent and virulent strains of Mycobacterium tuberculosis differentially induces the early genes c-fos, KC, JE, and tumor necrosis factor-alpha. Journal of Immunology, 150, 1886-1896.
Freund, J. (1956) The mode of action of immunologic adjuvants. Bibliography Tuberculosis, 10, 130-148.
Zuniga, J., Torres-Garcia, D., Santos-Mendoza, T., Rodriguez-Reyna, T.S., Granados, J. and Yunis, E.J. (2012) Cellular and humoral mechanisms involved in the control of tuberculosis. Clinical and Developmental Immunology, 2012, 1-18. doi:10.1155/2012/193923
Kaufmann, S.H. (1993) Immunity to intracellular bacteria. Annual Review of Immunology, 11, 129-163. doi:10.1146/annurev.iy.11.040193.001021
Collins, H.I. and Kaufmann, S.H. (2002) Acquired imunity against bacteria. In: Kaufmann, S.H., Ed., Immunology of Infectious Diseases, ASM Press, Washington DC, 207-221.
Petricevich, V.L., Ueda, C., Alves, R.C., da Silva, M.A., Moreno, C., Melo, A.R. and Dias da Silva, W. (2001) A single strain of Mycobacterium bovis bacillus Calmette- Guerin (BCG) grown in two different media evokes distinct humoral immune responses in mice. Brazilian Journal of Medical and Biological Research 34, 81-92. doi:S0100-879X2001000100010
Monteiro-Maia, R., Ortigao-de-Sampaio, M.B., Pinho, R.T. and Castello-Branco, L.R. (2006) Modulation of humoral immune response to oral BCG vaccination by Mycobacterium bovis BCG Moreau Rio de Janeiro (RDJ) in healthy adults. Journal of Immune Based Therapies and Vaccines, 4, 4. doi:10.1186/1476-8518-4-4
Nascimento, I.P., Dias, W.O., Mazzantini, R.P., Miyaji, E.N., Gamberini, M., Quintilio, W., Gebara, V.C., Cardoso, D.F., Ho, P.L., Raw, I., Winter, N., Gicquel, B., Rappuoli, R. and Leite, L.C. (2000) Recombinant Mycobacterium bovis BCG expressing pertussis toxin subunit S1 induces protection against an intracerebral challenge with live Bordetella pertussis in mice. Infection and Immunity, 68, 4877-4883. doi:10.1128/IAI.68.9.4877-4883.2000
Vasconcellos, H.L., Scaramuzzi, K., Nascimento, I.P., Da Costa Ferreira Jr., J.M., Abe, C.M., Piazza, R.M., Kipnis, A. and Dias da Silva, W. (2012) Generation of recombinant bacillus Calmette-Guerin and Mycobacterium smegmatis expressing BfpA and intimin as vaccine vectors against enteropathogenic Escherichia coli. Vaccine, 30, 5999-6005. doi:10.1016/j.vaccine.2012.05.083
Giles, A.R. (1987) Guidelines for the use of animals in biomedical research. Thrombosis and Haemostasis, 58, 1078-1084.
Remfry, J. (1987) Ethical aspects of animal experimentation. In: Tuffery, A.A., Ed., Laboratory Animals: An Introduction for New Experiments, Intersciences, New York, 5-9.
Steinbuch, M. and Audran, R. (1969) The isolation of IgG from mammalian sera with the aid of caprylic acid. Archives of Biochemistry and Biophysics, 134, 279-284. doi:10.1016/0003-9861(69)90285-9
Guidolin, R.G., Marcelino, R.M., Gondo, H.H., Morais, J.F., Ferreira, R.A., Silva, C.L., Kipnis, T.L., Silva, J.A., Fafetine, J. andDias da Silva, W. (2010) Polyvalent horse F(Ab')2 snake antivenom: Development of process to produce polyvalent horse F(Ab')2 antibodies anti-african snake venom. African Journal of Biotechnology, 9, 2446- 2455.
Cooper, A.M., Mayer-Barber, K.D. and Sher, A. (2011) Role of innate cytokines in mycobacterial infection. Mucosal Immunology, 4, 252-260. doi:10.1016/0003-9861(69)90285-9
Gonzalez-Navajas, J.M., Lee, J., David, M. and Raz, E. (2012) Immunomodulatory functions of type I interferons. Nature Reviews Immunology, 12, 125-135. doi:10.1038/nri3133
Desvignes, L., Wolf, A.J. and Ernst, J.D. (2012) Dynamic roles of type I and type II IFNs in early infection with Mycobacterium tuberculosis. Journal of Immunology, 188, 6205-6215. doi:10.4049/jimmunol.1200255
Kuhn, M., Goebel, W., Philpott, D.J. and Sansonetti, P.J. (2002) Overview of the bacterial pathogens. In: Kaufmann, S.H., Sher, A. and Ahmed, R., Eds., Immunology of Infectious Diseases, ASM Press, Washington, 5-23.
Novikov, A., Cardone, M., Thompson, R., Shenderov, K., Kirschman, K.D., Mayer-Barber, K.D., Myers, T.G., Rabin, R.L., Trinchieri, G., Sher, A. and Feng, C.G. (2011) Mycobacterium tuberculosis triggers host type I IFN signaling to regulate IL-1beta production in human macrophages. Journal of Immunology, 187, 2540-2547. doi:10.4049/jimmunol.1100926
Giacomini, E., Remoli, M.E., Gafa, V., Pardini, M., Fattorini, L. and Coccia, E.M. (2009) IFN-beta improves BCG immunogenicity by acting on DC maturation. Journal of Leukocyte Biology, 85, 462-468. doi:10.1189/jlb.0908583
Zhu, C., Lee, V., Finn, A., Senger, K., Zarrin, A.A., Du Pasquier, L. and Hsu, E. (2012) Origin of immunoglobulin isotype switching. Current Biology, 22, 872-880. doi:10.1016/j.cub.2012.03.060
Vidarsson, G., van Der Pol, W.L., van Den Elsen, J.M., Vile, H., Jansen, M., Duijs, J., Morton, H.C., Boel, E., Daha, M.R., Corthesy, B. and van De Winkel, J.G. (2001) Activity of human IgG and IgA subclasses in immune defense against Neisseria meningitidis serogroup B. Journal of Immunology, 166, 6250-6256.
Ravetch, J.V. and Kinet, J.P. (1991) Fc receptors. Annual Review of Immunology, 9, 457-492. doi:10.1146/annurev.iy.09.040191.002325
Garbett, N.D., Munro, C.S. and Cole, P.J. (1989) Opsonic activity of a new intravenous immunoglobulin preparation: Pentaglobin compared with sandoglobulin. Clinical & Experimental Immunology, 76, 8-12.
Armstrong, J.A. and Hart, P.D. (1971) Response of cultured macrophages to Mycobacterium tuberculosis, with observations on fusion of lysosomes with phagosomes. Journal of Experimental Medicine, 134, 713-740. doi:10.1084/jem.134.3.713
Deretic, V. and Fratti, R.A. (1999) Mycobacterium tuberculosis phagosome. Molecular Microbiology, 31, 1603- 1609. doi:10.1046/j.1365-2958.1999.01279.x
Shiloh, M.U., MacMicking, J.D., Nicholson, S., Brause, J.E., Potter, S., Marino, M., Fang, F., Dinauer, M. and Nathan, C. (1999) Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase. Immunity, 10, 29-38. doi:S1074-7613(00)80004-7
Encinales, L., Zuniga, J., Granados-Montiel, J., Yunis, M., Granados, J., Almeciga, I., Clavijo, O., Awad, C., Collazos, V., Vargas-Rojas, M.I., Banales-Mendez, J.L., Vazquez-Castaneda, L., Stern, J.N., Romero, V., Fridkis-Hareli, M., Terreros, D., Fernandez-Vina, M. and Yunis, E.J. (2010) Humoral immunity in tuberculin skin test anergy and its role in high-risk persons exposed to active tuberculosis. Molecular Immunology, 47, 1066-1073. doi:10.1016/j.molimm.2009.11.005
Nathan, C. (1997) Inducible nitric oxide synthase: What difference does it make? Journal of Clinical Investigation, 100, 2417-2423. doi:10.1172/JCI119782
Pereira, S.M., Dantas, O.M., Ximenes, R. and Barreto, M.L. (2007) BCG vaccine against tuberculosis: Its protective effect and vaccination policies. Revista de Saúde Pública, 41, 59-66.
Akira, S. and Takeda, K. (2004) Toll-like receptor signalling. Nature Reviews Immunology, 4, 499-511.
Yoneyama, M., Kikuchi, M., Natsukawa, T., Shinobu, N., Imaizumi, T., Miyagishi, M., Taira, K., Akira, S. and Fujita, T. (2004) The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nature Immunology, 5, 730-737.
Matzinger, P. (1994) Tolerance, danger, and the extended family. Annual Review of Immunology, 12, 991-1045. doi:10.1146/annurev.iy.12.040194.005015
Mallery, D.L., McEwan, W.A., Bidgood, S.R., Towers, G.J., Johnson, C.M. and James, L.C. (2010) Antibodies mediate intracellular immunity through tripartite motif- containing 21 (TRIM21). Proceedings of the National Academy of Sciences of the Untied States of America, 107, 19985-19990. doi:10.1073/pnas.1014074107
James, L.C., Keeble, A.H., Khan, Z., Rhodes, D.A. and Trowsdale, J. (2007) Structural basis for PRYSPRY-mediated tripartite motif (TRIM) protein function. Proceedings of the National Academy of Sciences of the Untied States of America, 104, 6200-6205. doi:10.1073/pnas.0609174104
Hauler, F., Mallery, D.L., McEwan, W.A., Bidgood, S.R. and James, L.C. (2012) AAA ATPase p97/VCP is essential for TRIM21-mediated virus neutralization. Proceedings of the National Academy of Sciences of the Untied States of America, 109, 19733-19738. doi:10.1073/pnas.1210659109
McEwan, W.A., Tam, J.C., Watkinson, R.E., Bidgood, S.R., Mallery, D.L. and James, L.C. (2013) Intracellular antibody-bound pathogens stimulate immune signaling via the Fc receptor TRIM21. Nature Immunology, 14, 327-336.