Zimmerman Daniel H, Rosenthal Ken S
Cel-Sci Corporation, 8229 Boone Blvd, Suite 802, Vienna, VA 22182, USA.
Front Biosci. 2005 Jan 1;10:790-8. doi: 10.2741/1572.
The Ligand Epitope Antigen Presentation System (L.E.A.P.S.) 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.
配体表位抗原呈递系统(L.E.A.P.S.)疫苗开发方法利用免疫肽来增强免疫原性,并影响针对可能过小而无法引发免疫反应的肽中表位所产生的免疫反应类型。这些免疫肽与抗原肽的共价连接促进了表位与T细胞(T细胞结合配体(TCBL))或抗原呈递细胞(免疫细胞结合配体(ICBL))的相互作用,并最终促进与CD4或CD8 T细胞上的T细胞受体结合。源自MHC I分子β2-微球蛋白链的J、ICBL/TCBL肽促进对抗原肽的Th1型反应,而源自MHC II分子β链的G、ICBL/TCBL肽促进Th2型反应。通过对L.E.A.P.S.疫苗免疫反应的表征以及通过引发对单纯疱疹病毒和其他病原体感染攻击的保护作用,已证明了这种方法的有效性。保护研究表明,L.E.A.P.S.方法允许定制适合诱导疾病保护的免疫反应。将讨论L.E.A.P.S.疫苗作用机制的理论、背景、实例和研究。