Towards identification of the mechanisms of action of parasite-derived peptide GK1 on the immunogenicity of an influenza vaccine.
Previous studies have shown that the synthetic peptide GK1, derived from Taenia crassiceps cysticerci, enhances the immunogenicity of the commercial inactivated influenza vaccine Fluzone in both young and aged mice. In particular, antibody responses were much improved. Since GK1 is a peptide and is rapidly cleared from the body, it offers the possibility to improve vaccine performance without undesirable effects. This study was therefore designed to understand the mechanisms of action involved in the adjuvant properties of GK1. For this, transgenic mice expressing a T-cell receptor specific for an epitope from the influenza virus hemagglutinin (HA) protein were employed. The GK1 peptide significantly increased the in vivo proliferative response of HA-specific CD4+ T cells when it was coimmunized with the HA epitope. Dendritic cells treated in vitro with GK1 were capable of enhancing T-cell activation. Furthermore, in synergy with lipopolysaccharide, GK1 enhanced the expression of major histocompatibility complex class II and costimulatory molecules of dendritic cells and promoted the secretion of proinflammatory cytokines and chemokines upon antigen-driven T-cell interaction. These data provide important insights into the mechanism that underlies the GK1 adjuvant capacity observed previously and underline the feasibility of using the transgenic mouse model described herein as a tool for investigation of the modes of action of different influenza vaccine adjuvants.
Segura-Velázquez
René
R
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, DF, México.
Fragoso
Gladis
G
Sciutto
Edda
E
Sarukhan
Adelaida
A
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006388:Hemagglutinins / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000494:pharmacology*; D010456:Peptides, Cyclic
D000276:Adjuvants, Immunologic; D018984:Epitopes, T-Lymphocyte; D006388:Hemagglutinins; D007252:Influenza Vaccines; D009842:Oligopeptides; D010456:Peptides, Cyclic; C534327:cyclo(cysteinyl-glycyl-aspargyl-seryl-aspargyl-prolyl-lysyl-seryl-cysteine)