title: Mycobacterial heat-shock proteins as carrier molecules. II: The use of the 70-kDa mycobacterial heat-shock protein as carrier for conjugated vaccines can circumvent the need for adjuvants and Bacillus Calmette Guérin priming.
abstract: In 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 with Mycobacterium tuberculosis var. bovis (bacillus Calmette-Guérin, BCG), for the induction of high and long-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 et al., 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 athymic nu/nu mice. 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 providing an 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 of IgG 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 design of new vaccines for eventual use in humans.
authors.affiliation: World Health Organization-Immunology Research and Training Center, Department of Pathology, University of Geneva, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Barrios
authors.forename: A R
authors.initials: AR
authors.lastname: Lussow
authors.forename: J
authors.initials: J
authors.lastname: Van Embden
authors.forename: R
authors.initials: R
authors.lastname: Van der Zee
authors.forename: R
authors.initials: R
authors.lastname: Rappuoli
authors.forename: P
authors.initials: P
authors.lastname: Costantino
authors.forename: J A
authors.initials: JA
authors.lastname: Louis
authors.forename: P H
authors.initials: PH
authors.lastname: Lambert
authors.forename: G
authors.initials: G
authors.lastname: Del Giudice
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology*; D001426:Bacterial Proteins; D018834:Chaperonin 60; D018833:Chaperonins; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D006001:Glycoconjugates; D006360:Heat-Shock Proteins / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D000922:Immunotoxins; D008288:Malaria / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008819:Mice, Nude; D008969:Molecular Sequence Data; D011135:Polysaccharides, Bacterial / Q000276:immunology / Q000302:isolation & purification; D015800:Protozoan Proteins; D011994:Recombinant Proteins / Q000276:immunology; D013997:Time Factors; D014611:Vaccination / Q000379:methods*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D001500:BCG Vaccine; D001426:Bacterial Proteins; D018834:Chaperonin 60; D006001:Glycoconjugates; D006360:Heat-Shock Proteins; D007074:Immunoglobulin G; D000922:Immunotoxins; D011135:Polysaccharides, Bacterial; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C041595:circumsporozoite protein, Protozoan; C074119:heat-shock protein 65, Mycobacterium; C037676:meningococcal group C polysaccharide; C028581:CRM197 (non-toxic variant of diphtheria toxin); D018833:Chaperonins