A randomized, controlled dose-finding Phase II study of the M72/AS01 candidate tuberculosis vaccine in healthy PPD-positive adults

Journal of Clinical Immunology

Volumn 33, Issue 8, 2013, Pages 1360-1375

  Montoya, Jaime ^a   Solon, Juan Antonio ^a   Cunanan, Soledad Rosanna C ^b   Acosta, Luz ^c   Bollaerts, Anne ^d   Moris, Philippe ^d   Janssens, Michel ^d   Jongert, Erik ^d   Demoitié, Marie Ange ^d   Mettens, Pascal ^d   Gatchalian, Salvacion ^a,e   Vinals, Carlota ^d   Cohen, Joe ^d   Ofori Anyinam, Opokua ^d  

^a UNIVERSITY OF THE PHILIPPINES MANILA   (Philippines)

^b Santa Rosa City Health Office I   (Philippines)

^c RESEARCH INSTITUTE FOR TROPICAL MEDICINE   (Philippines)

^d GSK   (Belgium)

^e GLAXOSMITHKLINE   (United Kingdom)

Author keywords

AS01; CD4+ T cells; M72 antigen; Tuberculosis; vaccine

Indexed keywords

BCG VACCINE; CD40 LIGAND; GAMMA INTERFERON; INTERLEUKIN 2; TUBERCULIN; TUMOR NECROSIS FACTOR ALPHA;

ADULT; ARTICLE; CD4+ T LYMPHOCYTE; CLINICAL EFFECTIVENESS; CONTROLLED STUDY; DISEASE ASSOCIATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; FEVER; FOLLOW UP; GASTROINTESTINAL SYMPTOM; HEADACHE; HUMAN; HUMORAL IMMUNITY; IMMUNE RESPONSE; IMMUNOGENICITY; INFECTION PREVENTION; INJECTION SITE PAIN; INJECTION SITE SWELLING; MALAISE; MALE; MYALGIA; OUTCOME ASSESSMENT; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL; SKIN REDNESS; SYNDROME DELINEATION; TUBERCULOSIS; VACCINE PRODUCTION;

ADJUVANTS, IMMUNOLOGIC; ADOLESCENT; ADULT; CD4-POSITIVE T-LYMPHOCYTES; DOSE-RESPONSE RELATIONSHIP, IMMUNOLOGIC; DRUG COMBINATIONS; FEMALE; HUMANS; IMMUNITY, CELLULAR; IMMUNITY, HUMORAL; LYMPHOCYTE COUNT; MALE; MIDDLE AGED; TUBERCULOSIS VACCINES; YOUNG ADULT;

EID: 84889091707     PISSN: 02719142     EISSN: 15732592     Source Type: Journal    
DOI: 10.1007/s10875-013-9949-3     Document Type: Article

References (57)

1. World Health Organization. Global Tuberculosis Control: WHO report 2012. Geneva, Switzerland: WHO; 2012. Report No.: WHO/HTM/TB/2012.6.
2. 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.
3. Fine PE. Variation in protection by BCG: implications of and for heterologous immunity. Lancet. 1995;346:1339-45.
4. Chan ED, Iseman MD. Current medical treatment for tuberculosis. BMJ. 2002;325:1282-6.
5. Weir RE, Gorak-Stolinska P, Floyd S, Lalor MK, Stenson S, Branson K, et al. Persistence of the immune response induced by BCG vaccination. BMC Infect Dis. 2008;8:9.
6. Sterne JA, Rodrigues LC, Guedes IN. Does the efficacy of BCG decline with time since vaccination? Int J Tuberc Lung Dis. 1998;2:200-7.
7. Anuradha B, Santosh CM, Hari Sai Priya V, Suman Latha G, Murthy KJ, Vijaya Lakshmi V. Age-related waning of in vitro interferon-γ levels against r32kDaBCG in BCG vaccinated children. J Immune Based Ther Vaccines. 2007;5:8.
8. Ottenhoff TH, Kaufmann SH. Vaccines against tuberculosis: where are we and where do we need to go? PLoS Pathog. 2012;8:e1002607.
9. + T cell responses to Mycobacterium tuberculosis in PPD-negative adults by M72/AS01 as compared to the M72/AS02 and Mbt72F/AS02 tuberculosis candidate vaccine formulations: a randomised trial. Vaccine. 2013;31:2196-206.
10. Garçon N, Chomez P, Van Mechelen M. GlaxoSmithKline Adjuvant Systems in vaccines: concepts, achievements and perspectives. Expert Rev Vaccines. 2007;6:723-39.
11. Garçon N, Van Mechelen M. Recent clinical experience with vaccines using MPL- and QS-21-containing Adjuvant Systems. Expert Rev Vaccines. 2011;10:471-86.
12. Skeiky YA, Alderson MR, Ovendale PJ, Guderian JA, Brandt L, Dillon DC, et al. Differential immune responses and protective efficacy induced by components of a tuberculosis polyprotein vaccine, Mtb72F, delivered as naked DNA or recombinant protein. J Immunol. 2004;172:7618-28.
13. Skeiky YA, Lodes MJ, Guderian JA, Mohamath R, Bement T, Alderson MR, et al. Cloning, expression, and immunological evaluation of two putative secreted serine protease antigens of Mycobacterium tuberculosis. Infect Immun. 1999;67:3998-4007.
14. Dillon DC, Alderson MR, Day CH, Lewinsohn DM, Coler R, Bement T, et al. Molecular characterization and human T-cell responses to a member of a novel Mycobacterium tuberculosis mtb39 gene family. Infect Immun. 1999;67:2941-50.
15. A candidate tuberculosis vaccine in Purified Protein Derivative-negative adults. Clin Vaccine Immunol. 2010;17:1763-71.
16. Spertini F, Audran R, Lurati F, Ofori-Anyinam O, Zysset F, Vandepapelière P, et al. The candidate tuberculosis vaccine Mtb72F/AS02 in PPD positive adults: a randomized controlled phase I/II study. Tuberculosis (Edinb). 2013;93:179-88.
17. Von Eschen K, Morrison R, Braun M, Ofori-Anyinam O, De Kock E, Pavithran P, et al. The candidate tuberculosis vaccine Mtb72F/AS02A: tolerability and immunogenicity in humans. Hum Vaccin. 2009;5:475-82.
18. A induces strong cross-reactive and polyfunctional CD4 T-cell responses. J Clin Immunol. 2011;31:443-54.
19. Maecker HT. Multiparameter flow cytometry monitoring of T cell responses. Methods Mol Biol. 2009;485:375-91.
20. Nomura L, Maino VC, Maecker HT. Standardization and optimization of multiparameter intracellular cytokine staining. Cytometry A. 2008;73:984-91.
21. + T cells with diverse cytokine profiles. Nat Med. 2005;11:1113-7.
22. + T cells specific for defined antigens according to CD154 expression. Nat Med. 2005;11:1118-24.
23. Hammarlund E, Lewis MW, Hansen SG, Strelow LI, Nelson JA, Sexton GJ, et al. Duration of antiviral immunity after smallpox vaccination. Nat Med. 2003;9:1131-7.
24. Flynn JL. Immunology of tuberculosis and implications in vaccine development. Tuberculosis (Edinb). 2004;84:93-101.
25. Flynn JL, Chan J. Immunology of tuberculosis. Annu Rev Immunol. 2001;19:93-129.
26. + multifunctional memory T cells coexpress GM-CSF. Cytokine. 2008;43:143-8.
27. Stenger S. Immunological control of tuberculosis: role of tumour necrosis factor and more. Ann Rheum Dis. 2005;64 Suppl 4:iv24-8.
28. Aagaard C, Hoang TT, Izzo A, Billeskov R, Troudt J, Arnett K, et al. Protection and polyfunctional T cells induced by Ag85B-TB10.4/IC31® against Mycobacterium tuberculosis is highly dependent on the antigen dose. PLoS One. 2009;4:e5930.
29. + T cell responses directed to dominant and subdominant epitopes in ESAT-6 from Mycobacterium tuberculosis. J Immunol. 2009;183:2659-68.
30. Hoang TT, Nansen A, Roy S, Billeskov R, Aagaard C, Elvang T, et al. Distinct differences in the expansion and phenotype of TB10.4 specific CD8 and CD4 T cells after infection with Mycobacterium tuberculosis. PLoS One. 2009;4:e5928.
31. Lindenstrom T, Agger EM, Korsholm KS, Darrah PA, Aagaard C, Seder RA, et al. Tuberculosis subunit vaccination provides long-term protective immunity characterized by multifunctional CD4 memory T cells. J Immunol. 2009;182:8047-55.
32. Aagaard C, Hoang T, Dietrich J, Cardona P-J, Izzo A, Dolganov G, et al. A multistage tuberculosis vaccine that confers efficient protection before and after exposure. Nat Med. 2011;17:189-94.
33. + T cells in adults. Am J Respir Crit Care Med. 2010;181:1407-17.
34. + memory T lymphocyte populations. Eur J Immunol. 2007;37:3089-100.
35. Hawkridge T, Scriba TJ, Gelderbloem S, Smit E, Tameris M, Moyo S, et al. Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in healthy adults in South Africa. J Infect Dis. 2008;198:544-52.
36. Sander CR, Pathan AA, Beveridge NE, Poulton I, Minassian A, Alder N, et al. Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in Mycobacterium tuberculosis-infected individuals. Am J Respir Crit Care Med. 2009;179:724-33.
37. + T cells. Eur J Immunol. 2010;40:279-90.
38. Scriba TJ, Tameris M, Mansoor N, Smit E, van der Merwe L, Mauff K, et al. Dose-finding study of the novel tuberculosis vaccine, MVA85A, in healthy BCG-vaccinated infants. J Infect Dis. 2011;203:1832-43.
39. Scriba TJ, Tameris M, Smit E, van der Merwe L, Hughes EJ, Kadira B, et al. A phase IIa trial of the new tuberculosis vaccine, MVA85A, in HIV- and/or Mycobacterium tuberculosis-infected adults. Am J Respir Crit Care Med. 2012;185:769-78.
40. Parida SK, Kaufmann SH. The quest for biomarkers in tuberculosis. Drug Discov Today. 2010;15:148-57.
41. Young JM, Adetifa IM, Ota MO, Sutherland JS. Expanded polyfunctional T cell response to mycobacterial antigens in TB disease and contraction post-treatment. PLoS One. 2010;5:e11237.
42. + T cells correlate with active Mycobacterium tuberculosis infection. Eur J Immunol. 2010;40:2211-20.
43. Kagina BM, Abel B, Scriba TJ, Hughes EJ, Keyser A, Soares A, et al. Specific T cell frequency and cytokine expression profile do not correlate with protection against tuberculosis after bacillus Calmette-Guérin vaccination of newborns. Am J Respir Crit Care Med. 2010;182:1073-9.
44. Rook GA, Dheda K, Zumla A. Immune systems in developed and developing countries; implications for the design of vaccines that will work where BCG does not. Tuberculosis (Edinb). 2006;86:152-62.
45. Rook GA, Dheda K, Zumla A. Immune responses to tuberculosis in developing countries: implications for new vaccines. Nat Rev Immunol. 2005;5:661-7.
46. Rook GA, Dheda K, Zumla A. Do successful tuberculosis vaccines need to be immunoregulatory rather than merely Th1-boosting? Vaccine. 2005;23:2115-20.
47. Rook GAW. Th2 cytokines in susceptibility to tuberculosis. Curr Mol Med. 2007;7:327-37.
48. Lalor MK, Smith SG, Floyd S, Gorak-Stolinska P, Weir RE, Blitz R, et al. Complex cytokine profiles induced by BCG vaccination in UK infants. Vaccine. 2010;28:1635-41.
49. Finan C, Ota MO, Marchant A, Newport MJ. Natural variation in immune responses to neonatal Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccination in a cohort of Gambian infants. PLoS One. 2008;3:e3485.
50. Djuardi Y, Sartono E, Wibowo H, Supali T, Yazdanbakhsh M. A longitudinal study of BCG vaccination in early childhood: the development of innate and adaptive immune responses. PLoS One. 2010;5:e14066.
51. + T lymphocytes. Eur J Immunol. 2001;31:1531-5.
52. Ruth JH, Warmington KS, Shang X, Lincoln P, Evanoff H, Kunkel SL, et al. Interleukin 4 and 13 participation in mycobacterial (type-1) and schistosomal (type-2) antigen-elicited pulmonary granuloma formation: multiparameter analysis of cellular recruitment, chemokine expression and cytokine networks. Cytokine. 2000;12:432-44.
53. Doherty TM, Kastelein R, Menon S, Andrade S, Coffman RL. Modulation of murine macrophage function by IL-13. J Immunol. 1993;151:7151-60.
54. Keyser A, Troudt JM, Taylor JL, Izzo AA. BCG sub-strains induce variable protection against virulent pulmonary Mycobacterium tuberculosis infection, with the capacity to drive Th2 immunity. Vaccine. 2011;29:9308-15.
55. Baldwin SL, Bertholet S, Reese VA, Ching LK, Reed SG, Coler RN. The importance of adjuvant formulation in the development of a tuberculosis vaccine. J Immunol. 2012;188:2189-97.
56. Pethe K, Alonso S, Biet F, Delogu G, Brennan MJ, Locht C, et al. The heparin-binding haemagglutinin of M. tuberculosis is required for extrapulmonary dissemination. Nature. 2001;412:190-4.
57. Abebe F, Bjune G. The protective role of antibody responses during Mycobacterium tuberculosis infection. Clin Exp Immunol. 2009;157:235-43.