The ability of heat-killed Mycobacterium vaccae to stimulate a cytotoxic T-cell response to an unrelated protein is associated with a 65 kilodalton heat-shock protein.
Exogenous antigens are generally presented by Class II major histocompatibility (MHC) molecules. When administered with an adjuvant, however, they are capable of inducing a CD8+ T-cell response where antigen recognition is associated with Class I MHC. Accordingly, immunization with soluble ovalbumin (OVA) alone does not activate CD8+ cytotoxic T cells (CTL) but when given in complete Freund's adjuvant (CFA), or in formulations of a number of novel adjuvants, an OVA-specific CD8+ CTL response can be detected. We show in this report that immunization with soluble OVA mixed with heat-killed Mycobacterium vaccae, but not with other common pathogenic and saprophytic mycobacteria, can activate OVA-specific CD8+ CTL. An OVA-specific CTL response is detected when mice are immunized by either the intraperitoneal or intranasal route and their spleen cells are re-stimulated in vitro. Adjuvant activity of heat-killed M. vaccae is present in M. vaccae culture filtrate, in soluble protein components of whole M. vaccae and in the 65 kDa heat-shock protein (hsp) of M. vaccae. Mycobacterium vaccae has previously been shown to have no adverse side-effects in humans. The current results suggest that M. vaccae may be useful as an adjuvant for vaccines and other immunotherapies where CD8+ CTL responses to exogenous proteins are crucial.
Genesis Research and Development Corporation Ltd, Auckland, New Zealand.
M A
MA
Skinner
R
R
Prestidge
S
S
Yuan
T J
TJ
Strabala
P L
PL
Tan
D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D007114:Immunization / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D009161:Mycobacterium / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; D015164:Vaccines, Inactivated; C074119:heat-shock protein 65, Mycobacterium; D010047:Ovalbumin; D018833:Chaperonins