The Ligand Epitope Antigen Presentation System ( L. E. A. P. S. TM) approach to vaccine development utilizes immune peptides to promote the immunogenicity and influence the type of immune response generated towards epitopes in peptides which may be too small to elicit an immune response. The covalent attachment of these immune peptides to the antigenic peptide promotes the interaction of the epitope with T cells ( T cell binding ligand (TCBL)) or antigen presenting cells ( immune cell binding ligand (ICBL)) and ultimately promotes binding with the T cell receptor on CD4 or CD8 T cells. The "J" ICBL/TCBL peptide derived from the beta-2-microglobulin chain of MHC I molecules promotes Th1 type responses to the antigenic peptide while the "G" ICBL/TCBL peptide derived from the beta chain of MHC II molecules promotes Th2 types of responses. The efficacy of this approach has been demonstrated by characterization of the immune responses to L. E. A. P. S. vaccines and by elicitation of protection from infectious challenge with herpes simplex virus and other pathogens. The protection studies show that the L. E. A. P. S. approach allows customization of the immune response appropriate for inducing protection from disease. The theory, background, examples and studies of the mechanism of action of the L. E. A. P. S. vaccines will be discussed.
LEAPS Vaccine Incorporating HER-2/neu Epitope Elicits Protection That Prevents and Limits Tumor Growth and Spread of Breast Cancer in a Mouse Model.
Creator
Rosenthal Ken S; Stone Sarah; Koski Gary; Zimmerman Daniel H
Publisher
Journal of immunology research
Date
2017
1905-07
Description
The prototype J-LEAPS T cell vaccine for HER-2/neu breast cancer (J-HER) consists of the murine HER-2/neu66-74 H-2(d) CD8 T cell epitope covalently attached through a triglycine linker to the J-immune cell binding ligand (ICBL) (human beta2 microglobulin38-50 peptide). The J-ICBL was chosen for its potential to promote Th1/Tc1 responses. In this proof-of-concept study, the ability of J-HER to prevent or treat cancer was tested in the TUBO cell-challenged BALB/c mouse model for HER-2/neu-expressing tumors. The J-HER vaccine was administered as an emulsion in Montanide ISA-51 without the need for a more potent adjuvant. When administered as a prophylactic vaccination before tumor challenge, J-HER protected against tumor development for at least 48 days. Despite eliciting protection, antibody production in J-HER-immunized, TUBO-challenged mice was less than that in unimmunized mice. More importantly, therapeutic administration of
Immunization with a LEAPS heteroconjugate containing a CTL epitope and a peptide from beta-2-microglobulin elicits a protective and DTH response to herpes simplex virus type 1.
Creator
Rosenthal K S; Mao H; Horne W I; Wright C; Zimmerman D
Publisher
Vaccine
Date
1999
1999-02
Description
A ligand epitope antigen presentation system (LEAPS) heteroconjugate vaccine containing a CTL epitope (H1) from the HSV-1 immediate early protein ICP27 (322-332) and a peptide sequence (J) from beta-2-microglobulin (35-50) elicited protection from intraperitoneal viral challenge and promoted DTH responses. The H1 peptide and other H1 containing heteroconjugates did not elicit protection or DTH responses. Antibody to the H1 peptide could not be detected by ELISA following vaccination with peptide, heteroconjugate or natural infection. The LEAPS heteroconjugate appears to prime a Thl-like response which is subsequently boosted by infection. These studies show that attachment of the J peptide can make a CTL epitope into a vaccine which is immunogenic and promotes a protective Th1 type of response.
Demethyleneberberine alleviates inflammatory bowel disease in mice through regulating NF-kappaB signaling and T-helper cell homeostasis.
Creator
Chen Yingying; Li Rui-Yan; Shi Mei-Jing; Zhao Ya-Xing; Yan Yan; Xu Xin-Xin; Zhang Miao; Zhao Xiao-Tong; Zhang Yu-Bin
Publisher
Inflammation research : official journal of the European Histamine Research Society ... [et al.]
Date
2017
2017-02
Description
OBJECTIVE: The activation of NF-kappaB signaling and unbalance of T-helper (Th) cells have been reported to play a key role in the pathogenesis of colitis. Cortex Phellodendri Chinensis (CPC) is commonly used to treat inflammation and diarrhea. Demethyleneberberine (DMB), a component of CPC, was reported to treat alcoholic liver disease as a novel natural mitochondria-targeted antioxidant in our previous study. In this study, we investigated whether DMB could protect against dextran sulfate sodium (DSS)-induced inflammatory colitis in mice by regulation of NF-kappaB pathway and Th cells homeostatis. METHODS: Inflammatory colitis mice were induced by 3% DSS, and DMB were orally administered on the doses of 150 and 300 mg/kg. In vitro, DMB (10, 20, 40 muM) and N-acetyl cysteine (NAC, 5 mM) were co-cultured with RAW264.7 for 2 h prior to lipopolysaccharide (LPS) stimulation, and splenocytes from the mice were cultured ex vivo for 48 h for immune response test. RESULTS: In vivo, DMB significantly alleviated the weight loss and diminished myeloperoxidase (MPO) activity, while significantly reduced the production of pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha), and inhibited the activation of