The BCG replacement vaccine VPM1002: From drawing board to clinical trial

Expert Review of Vaccines

Volumn 13, Issue 5, 2014, Pages 619-630

  Kaufmann, Stefan H E ^a   Cotton, Mark F ^b   Eisele, Bernd ^c   Gengenbacher, Martin ^a   Grode, Leander ^c   Hesseling, Anneke C ^b   Walzl, Gerhard ^b  

^a MAX PLANCK INSTITUTE FOR INFECTION BIOLOGY   (Germany)

^b STELLENBOSCH UNIVERSITY   (South Africa)

^c Vakzine Projekt Management GmbH ^*  (Germany)

Author keywords

bacille Calmette'Gu rin; listeriolysin O; Mycobacterium tuberculosis; pre exposure; prevention; prime vaccination; replacement; vaccine; VPM1002

Indexed keywords

BCG VACCINE; BCG VACCINE VPM1002; UNCLASSIFIED DRUG; VPM 10002;

BCG VACCINATION; BLADDER CANCER; CANCER PREVENTION; CLINICAL ASSESSMENT; DRUG EFFICACY; DRUG SAFETY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; IMMUNE RESPONSE; IMMUNOGENICITY; INFECTION PREVENTION; MESENTERIC LYMPHADENITIS; MORBIDITY; MORTALITY; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PRIORITY JOURNAL; REVIEW; TUBERCULOSIS; ANIMAL; CLINICAL TRIAL (TOPIC); DRUG EFFECTS; PHYSIOLOGY; TRENDS;

ANIMALS; BCG VACCINE; CLINICAL TRIALS AS TOPIC; HUMANS; MYCOBACTERIUM TUBERCULOSIS; TUBERCULOSIS;

EID: 84904006157     PISSN: 14760584     EISSN: 17448395     Source Type: Journal    
DOI: 10.1586/14760584.2014.905746     Document Type: Review

References (122)

1. WHO. Global Tuberculosis Report 2013. WHO Press; Geneva: 2013
2. WHO. Guidance for national tuberculosis programmes on the management of tuberculosis in children. 2006. Report No.: WHO/HTM/TB/2006.371
3. WHO. Roadmap for childhood tuberculosis: Towards zero deaths. WHO; Geneva: 2013; Report No.: WHO/HTM/TB/2013.12
4. Calmette A, Guérin C, Boquet A, Négre L. La vaccination préventive contre la tuberculose par le BCG. Masson; Paris: 1927
5. Barry CE III, Boshoff HI, Dartois V, et al. The spectrum of latent tuberculosis: Rethinking the biology and intervention strategies. Nat Rev Microbiol 2009;7: 845-55
6. Walzl G, Ronacher K, Hanekom W, et al. Immunological biomarkers of tuberculosis. Nat Rev Immunol 2011;11:343-54
7. Ulrichs T, Kaufmann SHE. New insights into the function of granulomas in human tuberculosis. J Pathol 2006;208:261-9
8. Reece ST, Kaufmann SH. Floating between the poles of pathology and protection: Can we pin down the granuloma in tuberculosis? Curr Opin Microbiol 2012;15:63-70
9. Gengenbacher M, Kaufmann SHE. Mycobacterium tuberculosis: Success through dormancy. FEMS Microbiol Rev 2012;36:514-32
10. O'Garra A, Redford PS, McNab FW, et al. The immune response in tuberculosis. Annu Rev Immunol 2013;31:475-527
11. Lawn SD, Myer L, Edwards D, et al. Short-Term and long-Term risk of tuberculosis associated with CD4 cell recovery during antiretroviral therapy in South Africa. AIDS 2009;23:1717-25
12. Khader SA, Bell GK, Pearl JE, et al. IL-23 and IL-17 in the establishment of protective pulmonary CD4(+) T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nat Immunol 2007;8:369-77
13. Green AM, Mattila JT, Bigbee CL, et al. CD4(+) regulatory T cells in a cynomolgus macaque model of Mycobacterium tuberculosis infection. J Infect Dis 2010;202:533-41
14. Stenger S, Hanson DA, Teitelbaum R, et al. An antimicrobial activity of cytolytic T cells mediated by granulysin. Science 1998;282: 121-5
15. Kaufmann SHE, Hussey G, Lambert PH. New vaccines for tuberculosis. Lancet 2010;375:85-94
16. Kaufmann SH. Tuberculosis vaccines: Time to think about the next generation. Semin Immunol 2013;25:172-81
17. Ottenhoff THM, Kaufmann SHE. Vaccines against tuberculosis: Where are we and where do we need to go? PLoS Pathog 2012;8:e1002607
18. Kaufmann SH, Gengenbacher M. Recombinant live vaccine candidates against tuberculosis. Curr Opin Biotechnol 2012;23:900-7
19. Calmette A, Guérin C. Recherches experimentales sur la defense de l'organisme contre l'infection tuberculeuse. Ann Inst Pasteur 1911;2:625-41
20. Dickie AW. BCG vaccination in Stockholm. Ulster Med J 1950;19:36-41
21. Cole ST, Brosch R, Parkhill J, et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 1998;393:537-44
22. Hesseling AC, Behr M. BCG: History, evolution, efficacy, and implications in the HIV era. Elsevier; London: 2009
23. Mahairas GG, Sabo PJ, Hickey MJ, et al. Molecular analysis of genetic differences between Mycobacterium bovis BCG and virulent M. bovis. J Bacteriol 1996;178: 1274-82
24. Behr MA, Small PM. A historical and molecular phylogeny of BCG strains. Vaccine 1999;17:915-22
25. Gordon SV, Brosch R, Billault A, et al. Identification of variable regions in the genomes of tubercle bacilli using bacterial artificial chromosome arrays. Mol Microbiol 1999;32:643-55
26. Brosch R, Gordon SV, Garnier T, et al. Genome plasticity of BCG and impact on vaccine efficacy. Proc Natl Acad Sci USA 2007;104:5596-601
27. Brodin P, Majlessi L, Marsollier L, et al. Dissection of ESAT-6 system 1 of Mycobacterium tuberculosis and impact on immunogenicity and virulence. Infect Immun 2006;74:88-98
28. Converse SE, Cox JS. A protein secretion pathway critical for Mycobacterium tuberculosis virulence is conserved and functional in Mycobacterium smegmatis. J Bacteriol 2005;187:1238-45
29. Simeone R, Bottai D, Brosch R. ESX/type VII secretion systems and their role in host-pathogen interaction. Curr Opin Microbiol 2009;12:4-10
30. Heimbeck J. Tuberculosis in hospital nurses. Tubercle 1936;18:97-9
31. Greenwood M. Professor Calmette's statistical study of B.C.G. vaccination. Br Med J 1928;1:793-5
32. Petroff SA. A new analysis of the value and safety of protective immunization with BCG (Bacillus Calmette-Guerin). Am Rev Tuberc 1929;20:275-96
33. WHO. BCG Vaccine. WHO position paper. Wkly Epidemiol Rec 2004;79:27-38
34. Zwerling A, Behr M, Verma A, et al. BCG Atlas: A database of global BCG vaccination policies and practices. PLoS Med 2011;8(3): E1001012
35. Wolzak NK, Cooke ML, Orth H, van TR. The changing profile of pediatric meningitis at a referral centre in Cape Town, South Africa. J Trop Pediatr 2012;58:491-5
36. Donald PR, van Zyl LE, de VJ. BCG vaccination status of children with tuberculous meningitis and the use of unsupervised isoniazid prophylaxis. S Afr Med J 1995;85:167-70
37. Lotte A, Wasz-Hockert O, Poisson N, et al. Second IUATLD study on complications induced by intradermal BCG-vaccination. Bull Int Union Tuberc Lung Dis 1988;63: 47-59
38. Hesseling AC, Johnson LF, Jaspan H, et al. Disseminated bacille Calmette-Guerin disease in HIV-infected South African infants. Bull World Health Organ 2009;87: 505-11
39. Nuttall JJ, Davies MA, Hussey GD, Eley BS. Bacillus Calmette-Guerin (BCG) vaccine-induced complications in children treated with highly active antiretroviral therapy. Int J Infect Dis 2008;12:e99-105
40. Rabie H, Violari A, Duong T, et al. Early antiretroviral treatment reduces risk of bacille Calmette-Guerin immune reconstitution adenitis. Int J Tuberc Lung Dis 2011;15:1194-200
41. Aaby P, Roth A, Ravn H, et al. Randomized trial of BCG vaccination at birth to low-birth-weight children: Beneficial nonspecific effects in the neonatal period? J Infect Dis 2011;204:245-52
42. Biering-Sorensen S, Aaby P, Napirna BM, et al. Small randomized trial among low-birth-weight children receiving bacillus Calmette-Guerin vaccination at first health center contact. Pediatr Infect Dis J 2012;31: 306-8
43. Fine PE, Smith PG, Evans SJ. Non-specific effects of BCG? J Infect Dis 2012;205: 515-18
44. Kleinnijenhuis J, Quintin J, Preijers F, et al. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci USA 2012;109:17537-42
45. Shann F. The non-specific effects of vaccines. Arch Dis Child 2010;95:662-7
46. Steenhuis TJ, van Aalderen WM, Bloksma N, et al. Bacille-Calmette-Guerin vaccination and the development of allergic disease in children: A randomized, prospective, single-blind study. Clin Exp Allergy 2008;38:79-85
47. Mostowy S, Tsolaki AG, Small PM, Behr MA. The in vitro evolution of BCG vaccines. Vaccine 2003;21:4270-4
48. Stevens JM, Galyov EE, Stevens MP. Actin-dependent movement of bacterial pathogens. Nat Rev Microbiol 2006;4: 91-101
49. van der Wel N, Hava D, Houben D, et al. Mycobacterium tuberculosis and Mycobacterium leprae translocate from the phagolysosome to the cytosol in myeloid cells. Cell 2007;129:1287-98
50. Hess J, Miko D, Catic A, et al. Mycobacterium bovis bacille Calmette-Guerin strains secreting listeriolysin of Listeria monocytogenes. Proc Natl Acad Sci USA 1998;95:5299-304
51. Palmer M. The family of thiol-Activated, cholesterol-binding cytolysins. Toxicon 2001;39:1681-9
52. Grode L, Seiler P, Baumann S, et al. Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guérin mutants that secrete listeriolysin. J Clin Invest 2005;115: 2472-9
53. Winau F, Weber S, Sad S, et al. Apoptotic vesicles crossprime CD8 T cells and protect against tuberculosis. Immunity 2006;24: 105-17
54. Farinacci M, Weber S, Kaufmann SH. The recombinant tuberculosis vaccine rBCG DeltaureC::hly(+) induces apoptotic vesicles for improved priming of CD4(+) and CD8 (+) T cells. Vaccine 2012;30:7608-14
55. Desel C, Dorhoi A, Bandermann S, et al. Recombinant BCG DeltaureC 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
56. Zhang SY, Boisson-Dupuis S, Chapgier A, et al. Inborn errors of interferon (IFN)-mediated immunity in humans: Insights into the respective roles of IFN-Alpha/beta, IFN-gamma, and IFN-lambda in host defense. Immunol Rev 2008;226:29-40
57. Velmurugan K, Grode L, Chang R, et al. Nonclinical development of BCG replacement vaccine candidates. Vaccines 2014;1:120-38
58. Grode L, Ganoza CA, Brohm C, et al. Safety and immunogenicity of the recombinant BCG vaccine VPM1002 in a phase 1 open-label randomized clnical trial. Vaccine 2013;31:1340-8
59. Morales A, Eidinger D, Bruce AW. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol 1976;116:180-3
60. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011;61: 69-90
61. European Cancer Observatory. Available from: Http://eco.iarc.fr
62. Babjuk M, Burger M, Zigeuner R, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: Update 2013. Eur Urol 2013;64:639-53
63. Herr HW, Schwalb DM, Zhang ZF, et al. Intravesical bacillus Calmette-Guerin therapy prevents tumor progression and death from superficial bladder cancer: Ten-year follow-up of a prospective randomized trial. J Clin Oncol 1995;13: 1404-8
64. Sylvester RJ. Bacillus Calmette-Guerin treatment of non-muscle invasive bladder cancer. Int J Urol 2011;18:113-20
65. Simons MP, O'Donnell MA, Griffith TS. Role of neutrophils in BCG immunotherapy for bladder cancer. Urol Oncol 2008;26:341-5
66. Zbar B, Rapp HJ. Immunotherapy of guinea pig cancer with BCG. Cancer 1974; 34(4 Suppl):1532-40.
67. Sun R, Skeiky YA, Izzo A, 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
68. Decatur AL, Portnoy DA. A PEST-like sequence in listeriolysin O essential for Listeria monocytogenes pathogenicity. Science 2000;290:992-5
69. Kupferschmidt K. Infectious disease. Taking a new shot at a TB vaccine. Science 2011;334:1488-90
70. Horwitz MA, Harth G, Dillon BJ, Maslesa-Galic S. Recombinant bacillus Calmette-Guerin (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 USA 2000;97:13853-8
71. Hoft DF, Blazevic A, Abate G, et al. A new recombinant bacille Calmette-Guerin vaccine safely induces significantly enhanced tuberculosis-specific immunity in human volunteers. J Infect Dis 2008;198:1491-501
72. Arbues A, Aguilo JI, Gonzalo-Asensio J, et al. Construction, characterization and preclinical evaluation of MTBVAC, the first live-Attenuated Mycobacterium tuberculosis-based vaccine to enter clinical trials. Vaccine 2013;31:4867-73
73. Goren MB, Brokl O, Schaefer WB. Lipids of putative relevance to virulence in Mycobacterium tuberculosis: Phthiocerol dimycocerosate and the attenuation indicator lipid. Infect Immun 1974;9:150-8
74. Kondo E, Kanai K. A suggested role of a host-parasite lipid complex in mycobacterial infection. Jpn J Med Sci Biol 1976;29: 199-210
75. Tameris MD, Hatherill M, Landry BS, et al. Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: A randomised, placebo-controlled phase 2b trial. Lancet 2013;381:1021-8
76. Frick M. The TB Vaccines Pipeline: Where are we going, where have we beeñ HIV i-Base and Treatment Action Group; London: 2013
77. Radosevic K, Wieland CW, Rodriguez A, et al. Protective immune responses to a recombinant adenovirus type 35 tuberculosis vaccine in two mouse strains: CD4 and CD8 T-cell epitope mapping and role of gamma interferon. Infect Immun 2007;75: 4105-15
78. Smaill F, Jeyanathan M, Smieja M, et al. A human type 5 adenovirus-based tuberculosis vaccine induces robust T cell responses in humans despite preexisting anti-Adenovirus immunity. Sci Transl Med 2013;5:205ra134
79. Aagaard C, Hoang T, Dietrich J, et al. A multistage tuberculosis vaccine that confers efficient protection before and after exposure. Nat Med 2011;17:189-94
80. Dietrich J, Aagaard C, Leah R, et al. Exchanging ESAT6 with TB10.4 in an Ag85B fusion molecule-based tuberculosis subunit vaccine: Efficient protection and ESAT6-based sensitive monitoring of vaccine efficacy. J Immunol 2005;174: 6332-9
81. van Dissel JT, Arend SM, Prins C, et al. Ag85B-ESAT-6 adjuvanted with IC31 promotes strong and long-lived Mycobacterium tuberculosis specific T cell responses in naive human volunteers. Vaccine 2010;28:3571-81
82. Montoya J, Solon JA, Cunanan SR, et al. A randomized, controlled dose-finding phase II study of the M72/AS01 candidate tuberculosis vaccine in healthy PPD-positive adults. J Clin Immunol 2013;33:1360-75
83. Leroux-Roels I, Forgus S, De BF, et al. Improved CD4(+) T cell responses to Mycobacterium tuberculosis in PPD-negative adults by M72/AS01 as compared to the M72/AS02 and Mtb72F/AS02 tuberculosis candidate vaccine formulations: A randomized trial. Vaccine 2013;31:2196-206
84. Bertholet S, Ireton GC, Ordway DJ, et al. A defined tuberculosis vaccine candidate boosts BCG and protects against multidrug-resistant Mycobacterium tuberculosis. Sci Transl Med 2010;2:53ra74
85. Malaga W, Perez E, Guilhot C. Production of unmarked mutations in mycobacteria using site-specific recombination. FEMS Microbiol Lett 2003;219:261-8
86. Rao M, Vogelzang A, Kaiser P, et al. The tuberculosis vaccine candidate bacillus Calmette-Guerin deltaureC::hly coexpressing human interleukin-7 or-18 enhances antigen-specific T cell responses in mice. PLoS One 2013;8:e78966
87. Aits S, Jaattela M. Lysosomal cell death at a glance. J Cell Sci 2013;126:1905-12
88. Burgdorf S, Kurts C. Endocytosis mechanisms and the cell biology of antigen presentation. Curr Opin Immunol 2008;20: 89-95
89. Reece ST, Kaufmann SH. Rational design of vaccines against tuberculosis directed by basic immunology. Int J Med Microbiol 2008;298:143-50
90. Velmurugan K, Chen B, Miller JL, et al. Mycobacterium tuberculosis nuoG is a virulence gene that inhibits apoptosis of infected host cells. PLoS Pathog 2007;3: E110
91. Hinchey J, Lee S, Jeon BY, et al. Enhanced priming of adaptive immunity by a proapoptotic mutant of Mycobacterium tuberculosis. J Clin Invest 2007;117: 2279-88
92. Braunstein M, Espinosa BJ, Chan J, et al. SecA2 functions in the secretion of superoxide dismutase A and in the virulence of Mycobacterium tuberculosis. Mol Microbiol 2003;48:453-64
93. Schneider BE, Korbel D, Hagens K, et al. A role for IL-18 in protective immunity against Mycobacterium tuberculosis. Eur J Immunol 2010;40:396-405
94. Maeurer MJ, Trinder P, Hommel G, et al. Interleukin-7 or interleukin-15 enhances survival of Mycobacterium tuberculosis-infected mice. Infect Immun 2000;68:2962-70
95. Appasamy PM. Interleukin-7: Biology and potential clinical applications. Cancer Invest 1993;11:487-99
96. Krawczenko A, Kieda C, Dus D. The biological role and potential therapeutic application of interleukin 7. Arch Immunol Ther Exp (Warsz) 2005;53:518-25
97. Melchionda F, Fry TJ, Milliron MJ, et al. Adjuvant IL-7 or IL-15 overcomes immunodominance and improves survival of the CD8+ memory cell pool. J Clin Invest 2005;115:1177-87
98. Ghayur T, Banerjee S, Hugunin M, et al. Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFNgamma production. Nature 1997;386: 619-23
99. Okamura H, Tsutsi H, Komatsu T, et al. Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 1995;378:88-91
100. Garcia VE, Uyemura K, Sieling PA, et al. IL-18 promotes type 1 cytokine production from NK cells and T cells in human intracellular infection. J Immunol 1999;162: 6114-21
101. Skopinski P, Rogala E, Duda-Krol B, et al. Increased interleukin-18 content and angiogenic activity of sera from diabetic (Type 2) patients with background retinopathy. J Diabetes Complications 2005;19:335-8
102. Dick T, Manjunatha U, Kappes B, Gengenbacher M. Vitamin B6 biosynthesis is essential for survival and virulence of Mycobacterium tuberculosis. Mol Microbiol 2010;78:980-8
103. Jackson M, Phalen SW, Lagranderie M, et al. Persistence and protective efficacy of a Mycobacterium tuberculosis auxotroph vaccine. Infect Immun 1999;67:2867-73
104. Sambandamurthy VK, Wang X, Chen B, et al. A pantothenate auxotroph of Mycobacterium tuberculosis is highly attenuated and protects mice against tuberculosis. Nat Med 2002;8:1171-4
105. Hondalus MK, Bardarov S, Russell R, et al. Attenuation of and protection induced by a leucine auxotroph of Mycobacterium tuberculosis. Infect Immun 2000;68: 2888-98
106. Pavelka MS Jr, Chen B, Kelley CL, et al. Vaccine efficacy of a lysine auxotroph of Mycobacterium tuberculosis. Infect Immun 2003;71:4190-2
107. Leyten EM, Lin MY, Franken KL, et al. Human T-cell responses to 25 novel antigens encoded by genes of the dormancy regulon of Mycobacterium tuberculosis. Microbes Infect 2006;8:2052-60
108. Betts JC, Lukey PT, Robb LC, et al. Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol Microbiol 2002;43:717-31
109. Schnappinger D, Ehrt S, Voskuil MI, et al. Transcriptional adaptation of Mycobacterium tuberculosis within macrophages: Insights into the phagosomal environment. J Exp Med 2003;198:693-704
110. Mollenkopf HJ, Grode L, Mattow J, et al. Application of mycobacterial proteomics to vaccine design: Improved protection by Mycobacterium bovis BCG prime-Rv3407 DNA boost vaccination against tuberculosis. Infect Immun 2004;72: 6471-9
111. Reece ST, Nasser-Eddine A, Dietrich J, 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
112. Chapman R, Chege G, Shephard E, et al. Recombinant Mycobacterium bovis BCG as an HIV vaccine vector. Curr HIV Res 2010;8:282-98
113. Matsumoto S, Yukitake H, Kanbara H, Yamada T. Recombinant Mycobacterium bovis bacillus Calmette-Guerin secreting merozoite surface protein 1 (MSP1) induces protection against rodent malaria parasite infection depending on MSP1-stimulated interferon gamma and parasite-specific antibodies. J Exp Med 1998;188:845-54
114. Arama C, Waseem S, Fernandez C, et al. A recombinant Bacille Calmette-Guerin construct expressing the Plasmodium falciparum circumsporozoite protein enhances dendritic cell activation and primes for circumsporozoite- specific memory cells in BALB/c mice. Vaccine 2012;30:5578-84
115. Fennelly GJ, Flynn JL, ter Meulen V, et al. Recombinant bacille Calmette-Guerin priming against measles. J Infect Dis 1995;172:698-705
116. Govan VA, Christensen ND, Berkower C, et al. Immunisation with recombinant BCG expressing the cottontail rabbit papillomavirus (CRPV) L1 gene provides protection from CRPV challenge. Vaccine 2006;24:2087-93
117. Langermann S, Palaszynski SR, Burlein JE, et al. Protective humoral response against pneumococcal infection in mice elicited by recombinant bacille Calmette-Guerin vaccines expressing pneumococcal surface protein A. J Exp Med 1994;180:2277-86
118. Edelman R, Palmer K, Russ KG, et al. Safety and immunogenicity of recombinant Bacille Calmette-Guerin (rBCG) expressing Borrelia burgdorferi outer surface protein A (OspA) lipoprotein in adult volunteers: A candidate Lyme disease vaccine. Vaccine 1999;17:904-14
119. Stover CK, Bansal GP, Hanson MS, et al. Protective immunity elicited by recombinant bacille Calmette-Guerin (BCG) expressing outer surface protein A (OspA) lipoprotein: A candidate Lyme disease vaccine. J Exp Med 1993;178:197-209
120. Arama C, Assefaw-Redda Y, Rodriguez A, et al. Heterologous prime-boost regimen adenovector 35-circumsporozoite protein vaccine/recombinant Bacillus Calmette-Guerin expressing the Plasmodium falciparum circumsporozoite induces enhanced long-Term memory immunity in BALB/c mice. Vaccine 2012;30:4040-5
121. Pethe K, Alonso S, Biet F, et al. The heparin-binding haemagglutinin of Mycobacterium tuberculosis is required for extrapulmonary dissemination. Nature 2001;412:190-4
122. Tchilian EZ, Desel C, Forbes EK, et al. Immunogenicity and protective efficacy against murine tuberculosis of prime-boost regimes with {Delta}ureC hly+ rBCG and MVA85A. Infect Immun 2009;77:622-31