title: Immunological basis of M13 phage vaccine: Regulation under MyD88 and TLR9 signaling.
abstract: Peptide-displaying bacteriophages induce mimotope-specific antibody responses, suggesting a novel application of phage-display library as bacteriophage vaccine. We examined the antibody response against M13 phage in mice induced by an i.p. administration of M13 phage in phosphate-buffered saline. We showed here that firstly, mice showed strong IgG antibody responses, particularly, in IgG2b, IgG2c, and IgG3 subclasses even in primary responses. Secondly, IgG production in primary response is totally dependent on MyD88 signaling. These responses were almost comparable, but slightly weaker, in TLR2-, TLR4- and TLR7-deficient mice relative to wild-type mice, suggesting that this enhancing effect is not due to plausible LPS contamination. Thirdly, although primary IgG1 response was not detected in wild-type mice, remarkable IgG1 response was induced in TLR9-deficient mice, suggesting that TLR9 pathway functions as regulatory, but not a simple augmenting signaling cascade, and furthermore, the enhanced IgG1 response was not due to adjuvant effect of single-stranded DNA derived from M13 phage. Thus, innate immunity including TLR regulation is crucial for M13 phage vaccine design.
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Science and Engineering, Kagoshima University, 1-21-40 Korimoto, Kagoshima 890-0065, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Hashiguchi
authors.forename: Yuya
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sugimura
mesh_terms: D000818:Animals; D017104:Bacteriophage M13 / Q000276:immunology*; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D019151:Peptide Library; D015398:Signal Transduction; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism*; D014612:Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G; D053594:Myeloid Differentiation Factor 88; D019151:Peptide Library; D051217:Toll-Like Receptor 9; D014612:Vaccines