Evidence for enhanced central memory priming by live Mycobacterium bovis BCG vaccine in comparison with killed BCG formulations.
Development of cattle vaccines against bovine tuberculosis is a GB research priority. Recently, it has been shown that formalin-killed Bacille Calmette-Guérin (BCG) delivered with the liposomal adjuvant NAX687 imparted significant protection against Mycobacterium bovis infection in the guinea pig aerosol infection model. Extending these studies, we inoculated calves with live BCG, formalin-killed BCG and formalin-killed BCG formulated in NAX687. Live and killed BCG vaccine formulations induced primary effector T-cell populations comparably, both killed BCG formulations also induced potent humoral immune responses. In contrast, live BCG generated enhanced central memory responses against the protective antigen Ag85A whilst killed BCG-induced such responses only poorly. However, the poor capacity of killed BCG to generate central memory could be partially overcome by formulation with NAX687. Measurement of central memory responses induced by TB vaccine candidates in cattle may provide a useful correlate of protection and warrants further investigation in challenge experiments.
Whelan
Adam O
AO
TB Research Group, Veterinary Laboratories Agency - Weybridge, New Haw, Addlestone, Surrey KT15 3NB, UK. a.o.whelan@vla.defra.gsi.gov.uk <a.o.whelan@vla.defra.gsi.gov.uk>
Wright
D Craig
DC
Chambers
Mark A
MA
Singh
Mahavir
M
Hewinson
R Glyn
RG
Vordermeier
H Martin
HM
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology; D001500:BCG Vaccine / Q000276:immunology*; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D009163:Mycobacterium bovis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary*; D014613:Vaccines, Attenuated / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D007074:Immunoglobulin G; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated; D007371:Interferon-gamma