Comparison of different delivery systems of vaccination for the induction of protection against tuberculosis in mice

The way to deliver antigens and cellular requirements for long-lasting prot ection against tuberculosis are not known. Immunizations with mycobacterial 65 kDa heat shock protein (hsp65) expressed from J774-hsp65 cells (antigen -presenting cells that endogenously produce hsp65 antigen) or from plasmid DNA, or with the protein entrapped in cationic liposomes. can each give pro tective immunity similar to that obtained from live Bacillus Calmette Gueri n (BCG), whereas injecting the protein in Freund's incomplete adjuvant (FIA ) has minimal effect. Protective procedures elicited high frequencies of an tigen-reactive rp T cells with CD4(+)/CD8(-) and CD8(+)/CD4(-) phenotypes. Protection correlated with the abundance of hsp65-dependent cytotoxic CD8()/CD4(-)/CD44(hi) cells. The frequency of these cells and the level of prot ection declined during 8 months after J774-hsp65 or liposome-mediated immun ization with hsp65 protein but were sustained or steadily increased over th is period after hsp65-DNA or BCG immunizations. IFN-gamma predominated over IL-4 among the hsp65-reactive CD8(+)/CD4(-) and CD4+/CD8(-) populations af ter J774-hsp65-, hsp65-liposome-, and hsp65-DNA-mediated immunizations, but similar levels of these cytokines prevailed after BCG vaccination. (C) 200 1 Elsevier Science Ltd. All rights reserved.