title: Flagellin fusion proteins as adjuvants or vaccines induce specific immune responses.
abstract: Vaccination is the most efficient prophylaxis against a variety of infectious diseases. New vaccination strategies rely on the incorporation of effective adjuvants, which stimulate the innate immune response and, in turn, activate the adaptive immune response. It is well established that flagellin induces inflammatory responses through the activation of antigen-presenting cells (APCs). In order to evaluate whether flagellin can serve as a carrier for the development of adjuvants or vaccines, we prepared a flagellin-enhanced green fluorescent protein (EGFP) fusion protein. Our results demonstrate that a flagellin-EGFP fusion protein is capable of stimulating APCs, resulting in the maturation of these cells and secretion of proinflammatory cytokines. Furthermore, APCs pulsed with the flagellin-EGFP fusion protein effectively process and present EGFP antigens. More importantly, animals immunized with the flagellin-EGFP fusion protein developed specific anti-EGFP T-cell responses. In contrast, recombinant EGFP was not able to stimulate APCs, nor did it induce a T-cell response. Thus, recombinant-flagellin fusion proteins may be suitable carriers as adjuvants or vaccines for the development of new vaccination strategies to induce and boost immune responses against infectious diseases and cancer.
authors.affiliation: Sidney Kimmel Cancer Center, San Diego, California 92121, USA.
authors.forename: Camilo
authors.initials: C
authors.lastname: Cuadros
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Lopez-Hernandez
authors.forename: Ana Lucia
authors.initials: AL
authors.lastname: Dominguez
authors.forename: Michael
authors.initials: M
authors.lastname: McClelland
authors.forename: Joseph
authors.initials: J
authors.lastname: Lustgarten
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005408:Flagellin / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology*; D049452:Green Fluorescent Proteins; D066298:In Vitro Techniques; D007249:Inflammation / Q000209:etiology; D008164:Luminescent Proteins / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D014612:Vaccines / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D014612:Vaccines; D005408:Flagellin; D049452:Green Fluorescent Proteins