The Immunomodulatory Effect of Heat Shock Protein 70: Immunization with a DNA Construct Based on the Malarial Antigen Fused with a Fragment of HSP 70 Primes for a Th‐1 Type of Response

Finding an appropriate adjuvant for human vaccination is crucial. Heat shock proteins (HSPs) act as adjuvants when coadministered with peptide antigens or given as fusion proteins. However, there is a potential risk of autoimmunity when using the complete molecules, because HSPs are evolutionary conserved. To overcome this, we first evaluated the adjuvant effect against two different antigens of a less-conserved fraction of Plasmodium falciparum HSP70 (Pf70C) and compared it to the whole HSP70 molecule from Trypanosoma cruzi (TcHSP70). We found that Pf70C exhibited similar adjuvant properties as the whole molecule. We later evaluated the adjuvant potential of Pf70C against the malarial antigen EB200 in a chimeric DNA construct. No appreciable levels of EB200-specific antibodies were detected in mice immunized only with the DNA constructs. However, DNA primed the immune system, because subsequent challenge with the corresponding recombinant fusion proteins elicited a strong Th-1 antibody response. In contrast, no priming effect was observed for ex vivo IFN-γ production but stimulation with the HSP-chimeric fusion protein induced a stronger secretion of IFN-γin vitro than other proteins used. These results indicate that the use of HSPs is promising in the design of new vaccines.