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)

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.

A Comparative Study of Stress-mediated Immunological Functions with the Adjuvanticity of Alum

“…This is supported by a previous report that inhibition of another HSP (HSP90) abrogated inflammasome formation (34). It is noteworthy that there is a great deal of evidence that exogenous HSP70 acts as an adjuvant (35)(36)(37)(38), which has been marred by criticism that the HSP70 used may have been contaminated with LPS, flaggelin, or nucleotides (39). This critique cannot be applied to the present work as exogenous HSP70 has not been used, but endogenous, inducible HSP70 was up-regulated by alum.…”

Mycobacterial heat shock protein 70 induces interleukin-10 production: immunomodulation of synovial cell cytokine profile and dendritic cell maturation

“…Mycobacterial heat shock protein 70 (MTBHSP70) has a number of immunological properties. It has been shown to be an excellent adjuvant for antibody production [6], as well as an extremely powerful antigen, even in lipopolysaccharide (LPS) hyporesponsive mice [7]. Finally, immunization with MTBHSP70 has been shown to protect against adjuvant arthritis in rats [8].…”

The heat shock proteins, Hsp70 and Hsp83, of Leishmania infantum are mitogens for mouse B cells

“…This hypothesis may be in line with the adjuvant properties showed by several microbial Hsps. In particular, it has been demonstrated that immunization with peptides or oligosaccharides conjugated to the Mycobacterium tuberculosis Hsp70 promotes a strong humoral response in the absence of adjuvants (Barrios et al 1992). Suzue and Young (1996) have further shown the immunogenic potential of M tuberculosis Hsp70 by immunizing mice with a recombinant human immunodeficiency virus type 1 p24-Hsp70 fusion protein.…”