Recombinant BCG: Innovations on an old vaccine. Scope of BCG strains and strategies to improve long-lasting memory

Frontiers in Immunology

Volumn 5, Issue APR, 2014, Pages

  da Costa, Adeliane Castro ^a   Nogueira, Sarah Veloso ^a   Kipnis, André ^a   Junqueira Kipnis, Ana Paula ^a  

^a FEDERAL UNIVERSITY OF GOIÁS   (Brazil)

Author keywords

Long term memory; Protection; rBCG; Strain differences; Tuberculosis; Vaccine

Indexed keywords

AG85 PROTEIN; BCG VACCINE; EARLY SECRETORY ANTIGENIC TARGET 6; GAMMA INTERFERON; HYBRID PROTEIN; INTERLEUKIN 2; LISTERIOLYSIN; MPT64 ANTIGEN; MYCOBACTERIUM ANTIGEN; RECOMBINANT VACCINE; SECRETORY PROTEIN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ANTIGEN EXPRESSION; ANTIGEN PRESENTATION; BACTERIAL LOAD; BCG VACCINATION; CD4+ T LYMPHOCYTE; CYTOKINE RELEASE; DRUG EFFICACY; GENE INSERTION; GENE OVEREXPRESSION; HUMAN; IMMUNE RESPONSE; IMMUNIZATION; IMMUNOGENICITY; IMMUNOLOGICAL MEMORY; NONHUMAN; PROTECTION; REVIEW; T LYMPHOCYTE; TUBERCULOSIS;

EID: 84900861650     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2014.00152     Document Type: Review

References (77)

1. Kamath AT, Fruth U, Brennan MJ, Dobbelaer R, Hubrechts P, Ho MM, et al. New live mycobacterial vaccines: the Geneva consensus on essential steps towards clinical development. Vaccine (2005) 23(29):3753-61. doi: 10.1016/j.vaccine.2005.03.001.
2. World Health Organization (WHO). Global Tuberculosis Control-Epidemiology, Strategy, Financing. Geneva: WHO (2009).
3. World Health Organization. Global Tuberculosis Control. Geneva: WHO (1998).
4. Partnership WST. The Global Plan to Stop TB 2011-2015: Transforming the Fight-Towards Elimination of Tuberculosis. Geneva: WHO (2010).
5. Aronson NF, Santosham M, Comstock GW, Haward RS, Moulton LH, Rhoades ER, et al. Long-term efficacy of BCG vaccine in American Indians and Alaska Natives: a 60-year follow-up study. JAMA (2004) 5:2086-91. doi:10.1001/jama.291.17.2086.
6. Mangtani P, Abubakar I, Arti C, Beynon R, Pimpin L, Fine PE, et al. Protection by BCG vaccine against tuberculosis: a systemic review of randomized controlled trials. Clin Infect Dis (2014) 58:470-80. doi:10.1093/cid/cit790.
7. WHO. Tuberculosis prevention trials: Madras (1979). Trial of BCG vaccines in South India for tuberculosis prevention. Bull World Health Organ (1979) 57:819-27.
8. Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV, et al. Efficacy of BCG vaccine in the prevention of tuberculosis: meta-analysis of the published literature. JAMA (1994) 271:698-702. doi:10.1001/jama.1994.03510330076038.
9. Trunz BB, Fine P, Dye C. Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness. Lancet (2006) 367:1173-80. doi:10.1016/S0140-6736(06)68507-3.
10. Calmette A, Guerin C, Ne'gre L, Boquet A. Premunition des nouveaux-nescontre la tuberculoseparlevaccin BCG, 1921-1926. Ann Inst Pasteur (Paris) (1926) 40:89-133.
11. Brosch R, Gordon SV, Pym A, Eiglmeier K, Garnier T, Cole ST. Comparative genomics of the mycobacteria. Int J Med Microbiol (2000) 290:143-52. doi:10.1016/S1438-4221(00)80083-1.
12. Joung SM, Ryoo S. BCG vaccine in Korea. Clin Exp Vaccine Res (2014) 2:83-91. doi:10.7774/cevr.2013.2.2.83.
13. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature (1998) 393:537-44. doi:10.1038/31159.
14. Behr MA, Wilson MA, Gill WP, Salamon H, Schoolnik GK, Rane S, et al. Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science (1999) 284:1520-3. doi:10.1126/science.284.5419.1520.
15. Honda I, Seki M, Ikeda N, Yamamoto S, Yano I, Koyama A, et al. Identification of two subpopulations of Bacillus Calmette-Guérin (BCG) Tokyo172 substrain with different RD16 regions. Vaccine (2006) 24:4969-74. doi:10.1016/j.vaccine.2006.03.055.
16. Leung AS, Tran V, Wu Z, Yu X, Alexander DC, Gao GF, et al. Novel genome polymorphisms in BCG vaccine strains and impact on efficacy. BMC Genomics (2008) 9:413. doi:10.1186/1471-2164-9-413.
17. Henao-Tamayo MI, Ordway DJ, Irwin SM, Shang S, Shanley C, Orme IM. Phenotypic definition of effector and memory T-lymphocyte subsets in mice chronically infected with Mycobacterium tuberculosis. Clin Vaccine Immunol (2010) 17:618-25. doi:10.1128/CVI.00368-09.
18. Junqueira-Kipnis AP, Turner J, Gonzalez-Juarrero M, Turner OC, Orme IM. Stable T-cell population expressing an effector cell surface phenotype in the lungs of mice chronically infected with Mycobacterium tuberculosis. Infect Immun (2004) 72(1):570-5. doi:10.1128/IAI.72.1.570-575.2004.
19. Kipnis A, Irwin S, Izzo AA, Basaraba RJ, Orme IM. Memory T lymphocytes generated by Mycobacterium bovis BCG vaccination reside within a CD4 CD44lo CD62 ligand (hi) population. Infect Immun (2005) 73:7759-64. doi:10.1128/IAI.73.11.7759-7764.2005.
20. Cooper AM, Dalton DK, Stewart TA, Griffin JP, Russell DG, Orme IM. Disseminated tuberculosis in interferon gamma gene-disrupted mice. J Exp Med (1993) 178:2243-7. doi:10.1084/jem.178.6.2243.
21. Flynn JL, Chan J, Triebold KJ, Dalton DK, Stewart TA, Bloom BR. An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J Exp Med (1993) 178:2249-54. doi:10.1084/jem.178.6.2249.
22. Ottenhoff TH. New pathways of protective and pathological host defense to mycobacteria. Trends Microbiol (2012) 20:419-28. doi:10.1016/j.tim.2012.06.002.
23. Desel C, Dorhoi A, Bandermann S, Grode L, Eisele B, Kaufmann SH. Recombinant BCG ΔureC hly+ induces superior protection over parental bcg by stimulating a balanced combination of type 1 and type 17 cytokine responses. J Infect Dis (2011) 204:1573-84. doi:10.1093/infdis/jir592.
24. +) T-cell memory responses induced by BCG vaccination of newborns. J Infect Dis (2013) 207(7):1084-94. doi:10.1093/infdis/jis941.
25. Jeong YH, Jeon BY, Gu SH, Cho SN, Shin SJ, Chang J, et al. Differentiation of antigen-specific T cells with limited functional capacity during Mycobacterium tuberculosis infection. Infect Immun (2014) 82:132-9. doi:10.1128/IAI.00480-13.
26. Behr MA, Small PM. Has BCG attenuated to impotence? Nature (1997) 389:133-4. doi:10.1038/38148.
27. Zhang W, Zhang Y, Zheng H, Pan Y, Liu H, Du P, et al. Genome sequencing and analysis of BCG vaccine strains. PLoS One (2013) 8(8):e71243. doi:10.1371/journal.pone.0071243.
28. Castillo-Rodal AI, Castañón-Arreola M, Hernándes-Pando R, Calva JJ, Sada-Díaz E, López-Vidal Y. Mycobacterium tuberculosis infection in a BALB/c model of progressive pulmonary tuberculosis. Infect Immun (2006) 74:1718-24. doi:10.1128/IAI.74.3.1718-1724.2006.
29. Davids V, Henakom WA, Mansoor N, Gamieldien H, Gelderbloem SJ, Hawkridge A, et al. The effect of bacilli Calmette-Guérin vaccine strain and rout of administration on induced immune responses in vaccinated infants. J Infect Dis (2006) 193:531-6. doi:10.1086/499825.
30. DasGupta SK, Jain S, Kaushal D, Tyagi AK. Expression systems for study of mycobacterial gene regulation and development of recombinant BCG vaccines. Biochem Biophys Res Commun (1998) 246:797-804. doi:10.1006/bbrc.1998.8724.
31. Lin CW, Su IJ, Chang JR, Chen YY, Lu JJ, Douh Y. Recombinant BCG coexpressing Ag85B, CFP10, and interleukin-12 induces multifunctional Th1 and memory T cells in mice. APMIS (2011) 120:72-82. doi:10.1111/j.1600-0463.2011.02815.x.
32. Tang C, Yamada H, Shibata K, Maeda N, Yoshida S, Wajjwalku W, et al. Efficacy of recombinant bacille Calmette-Guérin vaccine secreting interleukin-15/antigen 85B fusion protein in providing protection against Mycobacterium tuberculosis. J Infect Dis (2008) 197:1263-74. doi:10.1086/586902.
33. Sugawara I, Sun L, Mizuno S, Taniyama T. Protective efficacy of recombinant BCG Tokyo (Ag85A) in rhesus monkeys (Macaca mulatta) infected intratracheally with H37Rv Mycobacterium tuberculosis. Tuberculosis (2009) 89:62-7. doi:10.1016/j.tube.2008.09.008.
34. Sali M, Di Sante G, Cascioferro A, Zumbo A, Nicolo C, Dona V, et al. Surface expression of MPT64 as a fusion with the PE domain of PE_PGRS33 enhances Mycobacterium bovis BCG protective activity against Mycobacterium tuberculosis in mice. Infect Immun (2010) 78:5202-13. doi:10.1128/IAI.00267-10.
35. Tang C, Yamada H, Shibata K, Yoshida S, Wajjwalku W, Yoshikai Y. IL-15 protects antigen-specific CD8 T cell contraction after Mycobacterium bovis bacillus Calmette-Guérin infection. J Leukoc Biol (2009) 86:187-94. doi:10.1189/jlb.0608363.
36. + T cells. PLoS One (2012) 7:e32769. doi:10.1371/journal.pone.0032769.
37. Christy AJ, Dharman K, Dhandapaani G, Palaniyandi K, Gupta UD, Gupta P, et al. Epitope based recombinant BCG vaccine elicits specific TH1 polarized immune responses in BALB/c mice. Vaccine (2012) 30:1364-70. doi:10.1016/j.vaccine.2011.12.059.
38. Kong CU, Ng LG, Nambiar JK, Spratt JM, Weninger W, Triccas JA. Targeted induction of antigen expression within dendritic cells modulates antigen-specific immunity afforded by recombinant BCG. Vaccine (2011) 29:1374-81. doi:10.1016/j.vaccine.2010.12.070.
39. Shi C, Chen L, Chen Z, Zhang Y, Zhou Z, Lu J, et al. Enhanced protection against tuberculosis by vaccination with recombinant BCG over-expressing HspX protein. Vaccine (2010) 28:5237-44. doi:10.1016/j.vaccine.2010.05.063.
40. + cytolytic T-cell responses in lesions from Mycobacterium tuberculosis-infected primates. Mol Med (2012) 18:647-58. doi:10.2119/molmed.2011.00222.
41. Dey B, Jain R, Gupta UD, Katoch VM, Ramanathan VD, Tyagi AK. A booster vaccine expressing a latency-associated antigen augments BCG induced immunity and confers enhanced protection against tuberculosis. PLoS One (2011) 6(8):e23360. doi:10.1371/journal.pone.0023360.
42. Dey B, Jain R, Khera A, Gupta UD, Katoch VM, Ramanathan VD, et al. Latency antigen a-crystallin based vaccination imparts a robust protection against TB by modulating the dynamics of pulmonary cytokines. PLoS One (2011) 6(4):e18773. doi:10.1371/journal.pone.0018773.
43. Sun R, Skeiky YA, Izzo A, Dheenadhayalan V, Imam Z, Penn E, et al. Novel recombinant BCG expressing perfringolysin O and the over expression of key immunodominant antigens; pre-clinical characterization, safety and protection against challenge with Mycobacterium tuberculosis. Vaccine (2009) 27:4412-23. doi:10.1016/j.vaccine.2009.05.048.
44. Jain R, Dey B, Dhar N, Rao V, Singh R, Gupta UD, et al. Enhanced and enduring protection against tuberculosis by recombinant BCG-Ag85C and its association with modulation of cytokine profile in lung. PLoS One (2008) 3(12):e3869. doi:10.1371/journal.pone.0003869.
45. Qie YQ, Wang JL, Liu W, Shen H, Chen JZ, Zhu BD, et al. More vaccine efficacy studies on the recombinant bacille Calmette-Guérin co-expressing Ag85B, Mpt64 190-198 and Mtb8.4. Scand J Immunol (2009) 69:342-50. doi:10.1111/j.1365-3083.2009.02231.x.
46. Dey B, Jain R, Khera A, Rao V, Dhar N, Gupta UD, et al. Boosting with a DNA vaccine expressing ESAT-6 (DNAE6) obliterates the protection imparted by recombinant BCG (rBCGE6) against aerosol Mycobacterium tuberculosis infection in guinea pigs. Vaccine (2009) 28:63-70. doi:10.1016/j.vaccine.2009.09.121.
47. Lu Y, Xu Y, Yang E, Wang C, Wang H, Shen H. Novel recombinant BCG coexpressing Ag85B, ESAT-6 andRv2608 elicits significantly enhanced cellular immune and antibody responses in C57BL /6 Mice. Scand J Immunol (2012) 76:271-7. doi:10.1111/j.1365-3083.2012.02726.x.
48. Magalhães I, Sizemore DR, Ahmed RK, Mueller S, Wehlin L, Scanga C, et al. rBCG induces strong antigen-specific T cell responses in rhesus macaques in a prime-boost setting with an adenovirus 35 tuberculosis vaccine vector. PLoS One (2008) 3(11):e3790. doi:10.1371/journal.pone.0003790.
49. Hoft DF, Blazevic A, Abate G, Hanekom WA, Kaplan G, Soler JH, et al. A new recombinant bacille Calmette-Guérin vaccine safely induces significantly enhanced tuberculosis-specific immunity in human volunteers. J Infect Dis (2008) 198:1491-501. doi:10.1086/592450.
50. Tullius MV, Harth G, Maslesa-Galic S, Dillon BJ, Horwitz MA. A replication-limited recombinant Mycobacterium bovis BCG vaccine against tuberculosis designed for human immunodeficiency virus-positive persons is safer and more efficacious than BCG. Infect Immun (2008) 76:5200-14. doi:10.1128/IAI.00434-08.
51. Wang C, Fu R, Chen Z, Tan K, Chen L, Teng X, et al. Immunogenicity and protective efficacy of a novel recombinant BCG strain over expressing antigens Ag85A e Ag85B. Clin Dev Immunol (2012) 2012:1-9. doi:10.1155/2012/563838.
52. Deng YH, Sun Z, Yang XL, Bao L. Improved immunogenicity of recombinant Mycobacterium bovis bacillus Calmette-Guérin strains expressing fusion protein Ag85A-ESAT-6 of Mycobacterium tuberculosis. Scand J Immunol (2010) 72:332-8. doi:10.1111/j.1365-3083.2010.02444.x.
53. Deng YH, He HY, Zhang BS. Evaluation of protective efficacy conferred by a recombinant Mycobacterium bovis BCG expressing a fusion protein of Ag85A-ESAT-6. J Microbiol Immunol Infect (2012) 25:S1684-1182. doi:10.1016/j.jmii.2012.11.005.
54. Xu Y, Liu W, Shen H, Yan J, Qu D, Wang H. Recombinant Mycobacterium bovis BCG expressing the chimeric protein of antigen 85B and ESAT-6 enhances the Th1 cell-mediated response. Clin Vaccine Immunol (2009) 16:1121-6. doi:10.1128/CVI.00112-09.
55. Xu Y, Liu W, Shen H, Yan J, Yang E, Wang H. Recombinant Mycobacterium bovis BCG expressing chimeric protein of Ag85B and ESAT-6 enhances immunostimulatory activity of human macrophages. Microbes Infect (2010) 12:683-689. doi:10.1016/j.micinf.2010.04.002.
56. Yang X, Bao L, Deng Y. A novel recombinant Mycobacterium bovis bacillus Calmette-Guérin strain expressing human granulocyte macrophage colony-stimulating factor and Mycobacterium tuberculosis early secretory antigenic target 6 complex augments Th1 immunity. Acta Biochim Biophys Sin (2011) 43:511-8. doi:10.1093/abbs/gmr045.
57. +) T cells. Vaccine (2012) 30:7608-14. doi:10.1016/j.vaccine.2012.10.031.
58. Reece ST, Nasser-Eddine A, Dietrich J, Stein M, Zedler U, Schommer-Leitner S, et al. Improved long-term protection against Mycobacterium tuberculosis Beijing/W in mice after intra-dermal inoculation of recombinant BCG expressing latency associated antigens. Vaccine (2011) 29:8740-4. doi:10.1016/j.vaccine.2011.07.144.
59. Grode L, Ganoza CA, Brohm C, Weiner J, Eisele B, Kaufmann SH. Safety and immunogenicity of the recombinant BCG vaccine VPM1002 in phase 1 open-label randomized clinical trial. Vaccine (2013) 18:1340-8. doi:10.1016/j.vaccine.2012.12.053.
60. Ohara N, Ohara-Wada N, Kitaura H, Nishiyama T, Matsumoto S, Yamada T. Analysis of the genes encoding the antigen 85 complex and MPT51 from Mycobacterium avium. Infect Immun (1997) 65:3680-5.
61. Belisle JT, Vissa VD, Sievert T, Takayama K, Brennan PJ. Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis. Science (1997) 276:1420-2. doi:10.1126/science.276.5317.1420.
62. Horwitz MA, Harth G, Dillon BJ, Maslesa-Galic' S. Recombinant bacillus Calmette-Guérin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model. Proc Natl Acad Sci U S A (2000) 97:13853-8. doi:10.1073/pnas.250480397.
63. Horwitz MA, Harth G. A new vaccine against tuberculosis affords greater survival after challenge than the current vaccine in the guinea pig model of pulmonary tuberculosis. Infect Immun (2003) 71:1672-9. doi:10.1128/IAI.71.4.1672-1679.2003.
64. Harth G, Lee BY, Wang J, Clemens DL, Horwitz MA. Novel insights into genetics, biochemistry, and immunocytochemistry of the 30-kilodalton major extracellular protein of Mycobacterium tuberculosis. Infect Immun (1997) 64:3038-47.
65. Palma C, Iona E, Giannoni F, Pardini M, Brunori L, Fattorini L, et al. The LTK63 adjuvant improves protection conferred by Ag85B DNA-protein prime-boosting vaccination against Mycobacterium tuberculosis infection by dampening IFN-gamma response. Vaccine (2008) 26:4237-43. doi:10.1016/j.vaccine.2008.05.050.
66. Jackson M, Raynaud C, Lanéelle MA, Guilhot C, Laurent-Winter C, Ensergueix D, et al. Inactivation of the antigen 85C gene profoundly affects the mycolate content and alters the permeability of the Mycobacterium tuberculosis cell envelope. Mol Microbiol (1999) 31:1573-87. doi:10.1046/j.1365-2958.1999.01310.x.
67. Lozes E, Huygen K, Content J, Denis O, Montgomery DL, Yawman AM, et al. Immunogenicity and efficacy of a tuberculosis DNA vaccine encoding the components of the secreted antigen 85 complex. Vaccine (1997) 15:830-3. doi:10.1016/S0264-410X(96)00274-5.
68. Sugawara I, Udagawa T, Taniyama T. Protective efficacy of recombinant BCG Tokyo (Ag85A) BCG Tokyo with Ag85A peptide boosting against Mycobacterium tuberculosis-infected guinea pigs in comparison with that of DNA vaccine encoding Ag85A. Tuberculosis (2007) 87:94-101. doi:10.1016/j.tube.2006.05.001.
69. Sugawara I, Yamada H, Udagawa T, Huygen K. Vaccination of guinea pigs with DNA encoding Ag85A by gene gun bombardment. Tuberculosis (2003) 83:331-7. doi:10.1016/S1472-9792(03)00054-4.
70. Chang Z, Primm TP, Jakana J, Lee IH, Serysheva I, Chiu W, et al. Mycobacterium tuberculosis 16-kDa antigen (Hsp16.3) functions as an oligomeric structure in vitro to suppress thermal aggregation. J Biol Chem (1996) 12:7218-23.
71. Kong D, Kunimoto DY. Secretion of human interleukin 2 by recombinant Mycobacterium bovis BCG. Infect Immun (1995) 63:799-803.
72. +)-T-cell epitopes from antigen 85A. Infect Immun (2002) 70:1623-6. doi:10.1128/IAI.70.3.1623-1626.2002.
73. Schaible UE, Winau F, Sieling PA, Fischer K, Collins HL, Hagens K, et al. Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosis. Nat Med (2003) 9:1039-46. doi:10.1038/nm906.
74. Mandal M, Lee KD. Listeriolysin O-liposome mediated cytosolic delivery of macromolecule antigen in vivo: enhancement of antigen-specific cytotoxic T lymphocyte frequency, activity, and tumor protection. Biochim Biophys Acta (2002) 1563:7-17. doi:10.1016/S0005-2736(02)00368-1.
75. Kupferschmidt K. Infectious disease. Taking a new shot at a TB vaccine. Science (2011) 334:1488-90. doi:10.1126/science.334.6062.1488.
76. Hanekom WA. The immune response to BCG vaccination of newborns. Ann NY Acad Sci (2005) 1062:69-78. doi:10.1196/annals.1358.010.
77. World Health Organization (WHO). Global Tuberculosis Report. Geneva: WHO (2013).