Parenteral adenoviral boost enhances BCG induced protection, but not long term survival in a murine model of bovine TB.
Boosting BCG using heterologous prime-boost represents a promising strategy for improved tuberculosis (TB) vaccines, and adenovirus (Ad) delivery is established as an efficacious boosting vehicle. Although studies demonstrate that intranasal administration of Ad boost to BCG offers optimal protection, this is not currently possible in cattle. Using Ad vaccine expressing the mycobacterial antigen TB10.4 (BCG/Ad-TB10.4), we demonstrate, parenteral boost of BCG immunised mice to induce specific CD8(+) IFN-γ producing T cells via synergistic priming of new epitopes. This induces significant improvement in pulmonary protection against Mycobacterium bovis over that provided by BCG when assessed in a standard 4week challenge model. However, in a stringent, year-long survival study, BCG/Ad-TB10.4 did not improve outcome over BCG, which we suggest may be due to the lack of additional memory cells (IL-2(+)) induced by boosting. These data indicate BCG-prime/parenteral-Ad-TB10.4-boost to be a promising candidate, but also highlight the need for further understanding of the mechanisms of T cell priming and associated memory using Ad delivery systems. That we were able to generate significant improvement in pulmonary protection above BCG with parenteral, rather than mucosal administration of boost vaccine is critical; suggesting that the generation of effective mucosal immunity is possible, without the risks and challenges of mucosal administration, but that further work to specifically enhance sustained protective immunity is required.
Department of Bacteriology, Animal & Plant Health Agency (APHA), Woodham Lane, Addlestone, Surrey KT15 3NB, United Kingdom(1).
Daryan A
DA
Kaveh
Department of Bacteriology, Animal & Plant Health Agency (APHA), Woodham Lane, Addlestone, Surrey KT15 3NB, United Kingdom(1).
M Carmen
MC
Garcia-Pelayo
Department of Bacteriology, Animal & Plant Health Agency (APHA), Woodham Lane, Addlestone, Surrey KT15 3NB, United Kingdom(1).
Paul R
PR
Webb
Department of Bacteriology, Animal & Plant Health Agency (APHA), Woodham Lane, Addlestone, Surrey KT15 3NB, United Kingdom(1).
Esen E
EE
Wooff
Department of Bacteriology, Animal & Plant Health Agency (APHA), Woodham Lane, Addlestone, Surrey KT15 3NB, United Kingdom(1).
Véronique S
VS
Bachy
Department of Bacteriology, Animal & Plant Health Agency (APHA), Woodham Lane, Addlestone, Surrey KT15 3NB, United Kingdom(1). Electronic address: philip.hogarth@apha.gsi.gov.uk.
Philip J
PJ
Hogarth
D000256:Adenoviridae; D000281:Administration, Intranasal; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002417:Cattle; D005260:Female; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D014380:Tuberculosis, Bovine / Q000517:prevention & control*; D022223:Vaccines, Subunit / Q000276:immunology
D000942:Antigens, Bacterial; D001500:BCG Vaccine; C501710:TB10.4 antigen, Mycobacterium tuberculosis; D022223:Vaccines, Subunit; D007371:Interferon-gamma
Adenovirus; BCG; Parenteral vaccination; Prime-boost; Protection; Tuberculosis