A multistage tuberculosis vaccine that confers efficient protection before and after exposure.
All tuberculosis vaccines currently in clinical trials are designed as prophylactic vaccines based on early expressed antigens. We have developed a multistage vaccination strategy in which the early antigens Ag85B and 6-kDa early secretory antigenic target (ESAT-6) are combined with the latency-associated protein Rv2660c (H56 vaccine). In CB6F1 mice we show that Rv2660c is stably expressed in late stages of infection despite an overall reduced transcription. The H56 vaccine promotes a T cell response against all protein components that is characterized by a high proportion of polyfunctional CD4(+) T cells. In three different pre-exposure mouse models, H56 confers protective immunity characterized by a more efficient containment of late-stage infection than the Ag85B-ESAT6 vaccine (H1) and BCG. In two mouse models of latent tuberculosis, we show that H56 vaccination after exposure is able to control reactivation and significantly lower the bacterial load compared to adjuvant control mice.
Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark. caa@ssi.dk
Claus
C
Aagaard
Truc
T
Hoang
Jes
J
Dietrich
Pere-Joan
PJ
Cardona
Angelo
A
Izzo
Gregory
G
Dolganov
Gary K
GK
Schoolnik
Joseph P
JP
Cassidy
Rolf
R
Billeskov
Peter
P
Andersen
D000818:Animals; D000942:Antigens, Bacterial / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000627:therapeutic use; D004195:Disease Models, Animal; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects / Q000502:physiology; D007371:Interferon-gamma / Q000378:metabolism; D055985:Latent Tuberculosis / Q000188:drug therapy / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D032581:Tuberculosis Vaccines / Q000276:immunology / Q000627:therapeutic use*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000627:therapeutic use
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; C570849:Rv2660c protein, Mycobacterium tuberculosis; D032581:Tuberculosis Vaccines; D014614:Vaccines, Synthetic; D007371:Interferon-gamma
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