Protective immunity induced by peptide mimics to LPS in mice with endotoxic shock

Abstract

To characterize a mimotop, peptide mimic to epitope on lipopolysaccharide (LPS) which was named as 13L and was expected to induce humoral immune response to LPS and a protective immunity, peptide 13L was synthesized and conjugated to Blue Carrier (BC) as immunogen. Balb/c mice were immunized with peptide 13L - BC conjugate and BC only as control. Anti-LPS antibodies of mice immunized with peptide 13L-BC were detected by ELISA using peptide 13L-BSA as coating antigen. Survival time of mice challenged with S. typhi, and dynamics of MAP/mmHg in mice injected with LPS were observed. The results showed that specific antibodies against S. typhi-LPS 7261 and E. coli-LPS 2630 were elicited in mice immunized with peptide 13L-BC conjugate, and could be boosted by inactive bacterial and LPS. The main isotype of anti-LPS antibodies were IgG2a, IgG2b and IgM, but less IgG1 and IgG3, The survival time of mice infected with S. typhi were (12±1.3) days and (5.3± 0.4) days(P < 0.01) in group immunized with peptide 13L conjugate and with BC, respectively. And the peptide 13L-BC can also elicit protective immunity against endotoxic shock by LPS. The dynamics of MAP/mmHg observed by carotid Artery catheterization showed a significant difference between mice immunized with peptide 13L-BC and mice immunized with BC only in 1, 2,3 and 4 hours after injection of LPS 2630 (P < 0.05, P < 0.01, P < 0.05 and P < 0.01), and injection of LPS 7261 (P > 0.05, P < 0.05, P < 0.05 and P < 0.01). These results suggested that the peptide 13L can mimic the antigenicity of LPS epitopes to induce secondary antibody response like as thymus-dependent antigen, and also can elicit a protective immunity of mice from infection with G- bacteria and endotoxic shock. This peptide mimics could be a new vaccine candidate of LPS.