A tuberculosis vaccine based on phosphoantigens and fusion proteins induces distinct gammadelta and alphabeta T cell responses in primates.
Phosphoantigens are mycobacterial non-peptide antigens that might enhance the immunogenicity of current subunit candidate vaccines for tuberculosis. However, their testing requires monkeys, the only animal models suitable for gammadelta T cell responses to mycobacteria. Thus here, the immunogenicity of 6-kDa early secretory antigenic target-mycolyl transferase complex antigen 85B (ESAT-6-Ag85B) (H-1 hybrid) fusion protein associated or not to a synthetic phosphoantigen was compared by a prime-boost regimen of two groups of eight cynomolgus. Although phosphoantigen activated immediately a strong release of systemic Th1 cytokines (IL-2, IL-6, IFN-gamma, TNF-alpha), it further anergized blood gammadelta T lymphocytes selectively. By contrast, the hybrid H-1 induced only memory alphabeta T cell responses, regardless of phosphoantigen. These latter essentially comprised cytotoxic T lymphocytes specific for Ag85B (on average + 430 cells/million PBMC) and few IFN-gamma-secreting cells (+ 40 cells/million PBMC, equally specific for ESAT-6 and for Ag85B). Hence, in macaques, a prime-boost with the H-1/phosphoantigen subunit combination induces two waves of immune responses, successively by gammadelta T and alphabeta T lymphocytes.
Cendron
Delphine
D
Groupe d'Etude des Antigènes Non-Conventionnels, Unité 563 INSERM, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
Ingoure
Sophie
S
Martino
Angelo
A
Casetti
Rita
R
Horand
Françoise
F
Romagné
François
F
Sicard
Hélène
H
Fournié
Jean-Jacques
JJ
Poccia
Fabrizio
F
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D011756:Diphosphates / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D008252:Macaca fascicularis; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000517:prevention & control*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D011756:Diphosphates; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines; C429553:bromohydrin pyrophosphate