A novel atherogenic epitope from Mycobacterium tuberculosis heat shock protein 65 enhances atherosclerosis in rabbit and LDL receptor-deficient mice.

Previous studies have established that Mycobacterium tuberculosis heat shock protein 65 (mHSP65) plays an important role in immune-associated diseases as an autoimmune factor. Some overlapping epitopes of mHSP65 may serve as initiators of both atherosclerosis and other autoimmune-associated diseases. In the present study, atherosclerosis was significantly enhanced in high-cholesterol diet (HCD)-fed New Zealand white rabbits immunized with mHSP65(91-105) compared with PBS-immunized or BSA-immunized rabbits.

Improved efficacy of therapeutic vaccination with dendritic cells pulsed with tumor cell lysate against hepatocellular carcinoma by introduction of 2 tandem repeats of microbial HSP70 peptide epitope 407-426 and OK-432.

Therapeutic vaccination with dendritic cells (DCs) pulsed with tumor cell lysate vaccine (H-D) represents an attractive approach for hepatocellular carcinoma (HCC) treatment. However, the efficacy of this approach is not most satisfactory for the low levels of T helper 1 (Th1)-type cytokines secretion and weak T cell responses. In this study, in order to increase the potency of H-D, two tandem repeats of microbial HSP70 peptide epitope 407-426 (2mHSP70(407-426), M2) which has been demonstrated to be effective in enhancing DC maturation were applied.

Immunization with P277 induces vascular leak syndrome in C57BL/6 mice via endothelial damage.

Accumulating evidence established a positive association of anti-heat shock protein 60 (HSP60) autoantibodies and the presence of atherosclerosis. However, whether anti-P277 (HSP60 437-460) autoantibodies may lead to the pathological increase in vascular permeability, a vascular leak syndrome (VLS), is unknown. In the present study, anti-P277 immunity was effectively induced in C57BL/6 mice, causing a marked increase in VLS in both normal mice and those bearing melanoma as well.

Vaccination with a potent DNA vaccine targeting B-cell epitopes of hGRP induces prophylactic and therapeutic antitumor activity in vivo.

Gastrin-releasing peptide (GRP), a bombesin-like peptide, is an autocrine or paracrine growth factor that can stimulate the growth of various cancer cells, making it an ideal target antigen to develop vaccines against cancer. In this study, we developed a novel DNA vaccine that encodes six tandem repeats of B-cell epitope GRP(18-27) (GRP6) flanked by HSP65 as carrier and four tandem repeats of mycobacterial HSP70(407-426) (M4) as helper T-cell epitopes for enhancement of immunogenicity. When intramuscularly immunized to mice, this anti-GRP DNA vaccine-induced GRP-specific antibody (Ab) responses that were at least 10-fold higher in magnitude compared with HSP65-GRP6 protein vaccine.

The fusion protein of HSP65 with tandem repeats of beta-hCG acting as a potent tumor vaccine in suppressing hepatocarcinoma.

It has been demonstrated that the beta-subunit of human chorionic gonadotropin (beta-hCG) is ectopically expressed on a variety of human cancers of different histological types and has been used as an antigenic target in anti-cancer vaccines. We engineered a fusion protein by fusing 10 tandemly repeated copies of the 10-residue sequence of beta-hCG (109-118) (in CTP37) combined with beta-hCG C-terminal 37 peptides to mycobacterial heat-shock protein 65 and immunized mice via subcutaneous injection. Humoral immune and cellular immune responses were effectively elicited.

Strong humoral response elicited by a DNA vaccine targeting gastrin-releasing peptide with optimized adjuvants inhibits murine prostate carcinoma growth in vivo.

Previous studies demonstrated that the elevated expression and receptor binding of gastrin-releasing peptide (GRP) in various types of cancer suggest that GRP might be a putative target for immunotherapy in neoplastic diseases. DNA vaccine for hormone/growth factor immune deprivation represents a feasible and attractive approach for cancer treatment; nevertheless, there is still a need to increase the potency of the DNA vaccine. Here, based on six copies of the B cell epitope GRP(18-27) in a linear alignment as an immunogen, we designed several anti-GRP DNA vaccines containing different combinations of immunoadjuvants, such as HSP65, tetanus toxoid(830-844) (T), pan HLA-DR-binding epitope (PADRE) (P), and mycobacterial HSP70(407-426) (M), on a backbone of pCR3.

Improved efficacy of DNA vaccination against prostate carcinoma by boosting with recombinant protein vaccine and by introduction of a novel adjuvant epitope.

DNA vaccine represents an attractive approach for cancer treatment by inducing active immune-deprivation of gastrin-releasing peptide (GRP) from tumor cells, the growth of which is dependent on the stimulation of GRP. In this study, we developed a DNA vaccine using a plasmid vector to deliver the immunogen of six copies of the B cell epitope GRP(18-27) (GRP6). In order to increase the potency of this DNA vaccine, multiple strategies have been applied including DNA-prime protein-boost immunization and introduction of a foreign T-helper epitope into DNA vaccine.