Mycobacterial heat‐shock proteins as carrier molecules. II: The use of the 70‐kDa mycobacterial heat‐shock protein as carrier for conjugated vaccinescan circumvent the need for adjuvants and Bacillus Calmette Guérin priming)

摘要

AbstractIn a recent work, we have shown that mycobacterial heat‐shock proteins (hsp)of 65‐kDa (GroEL‐type) and 70‐kDa (DnaK‐type) acted as carrier molecules in mice, previously primed withMycobacterium tuberculosisvar.bovis(bacillus Calmette‐Guérin, BCG), for the induction of high andlong‐lasting titers of IgG against the repetitive malaria synthetic peptide (NANP)40. Anti‐peptide antibodies were induced when the malaria peptide, conjugated to the mycobacterial hsp, was given in the absence of any adjuvants (Lussow etal.,Eur. J. Immunol.1991.87:2960). In this report, we show that mice immunized with peptides or oligosaccharides conjugated to the 70‐kDa hsp produced high titers of IgG antibodies in the absence of any previous priming with BCG.The anti‐peptide antibody response persisted for at least 1 year. This adjuvant‐free carrier effect of the 70‐kDa hsp was T cell dependent, since no anti‐peptide nor anti‐70‐kDa IgG antibodies were induced in athymicnu/numice. Previous immunization of mice with the 65‐kDa or 70‐kDa hsp did not have any negative effect on the induction of anti‐peptide IgG antibodies after immunization with hsp‐peptide conjugates in the absence of adjuvants. Furthermore, preimmunization with the 65‐kDa hsp could substitute for BCG in providingan effective priming for the induction of anti‐(NANP) antibodies. Finally, both the 65‐kDa and 70‐kDa hsp acted as carrier molecules for the induction ofIgG antibodies to group C meningococcal oligosaccharides, in the absence of adjuvants. These findings strongly suggest that the use of hsp as carriers in conjugated constructs for the induction of anti‐peptide and anti‐oligosaccharide antibodies could be of value in the