title: ESAT-6 subunit vaccination against Mycobacterium tuberculosis.
abstract: The ESAT-6 antigen from Mycobacterium tuberculosis is a dominant target for cell-mediated immunity in the early phase of tuberculosis (TB) in TB patients as well as in various animal models. The purpose of our study was to evaluate the potential of ESAT-6 in an experimental TB vaccine. We started out using dimethyl dioctadecylammonium bromide (DDA), an adjuvant which has been demonstrated to be efficient for the induction of cellular immune responses and has been used successfully before as a delivery system for TB vaccines. Here we demonstrate that, whereas immune responses to both short-term-culture filtrate and Ag85B are efficiently induced with DDA, this adjuvant was inefficient for the induction of immune responses to ESAT-6. Therefore, we investigated the modulatory effect of monophosphoryl lipid A (MPL), an immunomodulator which in different combinations has demonstrated strong adjuvant activity for both cellular and humoral immune responses. We show in the present study that vaccination with ESAT-6 delivered in a combination of MPL and DDA elicited a strong ESAT-6-specific T-cell response and protective immunity comparable to that achieved with Mycobacterium bovis BCG.
authors.affiliation: Department of TB Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Brandt
authors.forename: M
authors.initials: M
authors.lastname: Elhay
authors.forename: I
authors.initials: I
authors.lastname: Rosenkrands
authors.forename: E B
authors.initials: EB
authors.lastname: Lindblad
authors.forename: P
authors.initials: P
authors.lastname: Andersen
mesh_terms: D000217:Acyltransferases; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins; D001428:Bacterial Vaccines / Q000276:immunology*; D003634:DDT / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D008050:Lipid A / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D008050:Lipid A; C000849:bis(p-chlorophenyl)acetic acid; D003634:DDT; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis; C048436:monophosphoryl lipid A