title: Peptide mimotopes as prototypic templates of broad-spectrum surrogates of carbohydrate antigens.
abstract: Peptide mimetics of carbohydrate antigens can function as templates to exploit immune mechanisms to augment vaccine design strategies as they are T cell dependent antigens. In this study we evaluate a peptide mimetic (peptide 105) of the Pneumococcal capsular polysaccharide type 14 (Pn14) as a model antigen to explore differences in antigenicity and immunogenicity of peptide mimotopes. The multiple antigenic peptide (MAP) form, by ELISA, competes with native Pn14 in a concentration-dependent manner for binding to an anti-Pn14 monoclonal antibody. It was observed that peptide priming with a conjugated form (105-BSA) and boosting with Pn14 produced higher levels of Pn14-reactive IgG1, IgG2a, IgG2b and IgG3 than priming and boosting with Pn14. This serum also displayed reactivity with multiple serotypes, as assessed by ELISA. However, when compared with serum from humans immunized with the 23-valent pneumococcal vaccines, mimetic-induced mouse serum did not display a significant ability to mediate opsonophagocytic killing of pneumococci. These results suggest the feasibility of designing mimotopes to render effective humoral responses not only to a single serotype of Streptococcus pneumoniae, but to multiple serotypes at once. Such peptides would simplify currently available vaccine approaches, yet highlights the requirement of more extensive polymerization to fully emulate native antigen.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: G
authors.initials: G
authors.lastname: Cunto-Amesty
authors.forename: P
authors.initials: P
authors.lastname: Luo
authors.forename: B
authors.initials: B
authors.lastname: Monzavi-Karbassi
authors.forename: A
authors.initials: A
authors.lastname: Lees
authors.forename: J
authors.initials: J
authors.lastname: Alexander
authors.forename: M F
authors.initials: MF
authors.lastname: del Guercio
authors.forename: M H
authors.initials: MH
authors.lastname: Nahm
authors.forename: C
authors.initials: C
authors.lastname: Artaud
authors.forename: J
authors.initials: J
authors.lastname: Stanley
authors.forename: T
authors.initials: T
authors.lastname: Kieber-Emmons
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D016667:Bacterial Capsules / Q000276:immunology; D002241:Carbohydrates / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D011485:Protein Binding
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D002241:Carbohydrates; D010455:Peptides; C056696:pneumococcal polysaccharide, type 14