Immunological basis of M13 phage vaccine: Regulation under MyD88 and TLR9 signaling

Hashiguchi, Shuhei; Yamaguchi, Yuya; Takeuchi, Osamu; Akira, Shizuo; Sugimura, Kazuhisa

doi:10.1016/j.bbrc.2010.09.094

Cited by 49 publications

(47 citation statements)

References 20 publications

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“…In fact, to the best of our knowledge, there are only two studies to suggest that phage virions can stimulate TLRs. In the first study, mice deficient in MyD88, a protein essential for signaling through all TLRs (except TLR3), unlike wild-type mice, did not respond to M13 phage immunization [54]. The second study was performed on a murine model of melanoma and showed that bacteriophageinduced tumor regression, production of proinflammatory cytokines and chemokines by tumor-infiltrating macrophages, and neutrophil infiltration of tumors were almost completely abolished in MyD88-deficient mice compared with wild-type mice [55].…”

Section: • Phages and Inflammationmentioning

confidence: 99%

Phages and Immunomodulation

et al. 2017

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In the past years, the microbiome and its role in the pathophysiology of diseases have gained great interest. The progress of our knowledge in this field opens completely novel prospects for treating disorders, including those which are most challenging to medicine today. Of special interest are studies on the interactions of the microbiome with the immune system. Only recently has the presence of bacteriophages in the microbiome been highlighted, and their potential role in maintaining normal immunity has gained increasing attention. We summarize the available data pointing to the potential impact of phages in maintaining immunological homeostasis.

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Section: • Phages and Inflammationmentioning

confidence: 99%

Phages and Immunomodulation

et al. 2017

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“…Therefore, B-cell epitope-based mimotopes may represent a more universal vaccine concept. For phage-displayed mimotopes, the immunogenic mechanism in mice has been recently identified as being regulated under MyD88 and depending on TLR-9 signaling, independent on CpG contamination in the phage preparations [91]. Being processed and presented by antigen-presenting cells, the immune response towards mimotopes depends on T-helper cells providing bystander help [92], whereas the B-cell mimotopes rarely contain antigen-specific T-cell epitopes [77].…”

Section: The Principle Of Mimotope Vaccinesmentioning

confidence: 99%

Cancer vaccines inducing antibody production: more pros than cons

Jensen‐Jarolim¹,

Singer²

2011

Expert Review of Vaccines

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“…It is extremely immunogenic, eliciting high titer serum Abs after a single immunization without adjuvant; 15,18,19 the particulate nature of the phage as well as virion-associated bacterial lipopolysaccharide (LPS), 20 likely contribute to its immunogenicity. 21 While the Ab response to phage is T-cell driven, 22 it may also act as a thymusindependent antigen, eliciting an early burst of ASCs in the blood and spleen two days after immunization (our unpublished results), probably due to cross linking of Escherichia coli. The phage genome is composed of a single-stranded DNA circle encased in a rod-like protein capsid composed almost entirely of ~2,700-4,000 overlapping copies of the major coat protein, pVIII, with ~5 molecules of the minor coat proteins pIII, pVI, pVII and pIX positioned on opposite ends of the particle ( Fig.…”

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confidence: 80%

Developing strategies to enhance and focus humoral immune responses using filamentous phage as a model antigen

et al. 2011

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Filamentous bacteriophage are commonly used as immunogenic carriers for peptides and proteins displayed on the phage surface. Previously, we showed that immunization with phage to which peptides had been chemically conjugated can elicit a focused anti-peptide antibody response compared with traditional carrier molecules bearing the same peptide, perhaps due to the low surface complexity of the phage. The regularity of its surface also gives the phage other advantages as a carrier, including immunological simplicity and thousands of well-defined sites for chemical conjugation. More recently, we showed that focusing of antibody responses against 'target' peptides was enhanced when the phage's molecular surface was simplified by removal of immunodominant B-cell epitopes present on the minor coat protein, pIII. The pIII-truncated variant elicits an antibody response that is largely restricted to the exposed N-terminus of the major coat protein, pVIII, and to phage-associated bacterial lipopolysaccharide, and a significant fraction of this response crossreacts with a 12-residue peptide covering the surface-exposed region of pVIII. This allows one to track antibody responses against the phage (and any associated haptens) as they develop over time, and characterize them using a combination of serological, flow cytometric, cellular and immunogenetic assays. The filamentous phage thus provides an excellent model system for studying various aspects of the antibody response, all with the goal of targeting antibody production against weakly immunogenic peptides, proteins and carbohydrates.

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Immunological basis of M13 phage vaccine: Regulation under MyD88 and TLR9 signaling

Cited by 49 publications

References 20 publications

Phages and Immunomodulation

Phages and Immunomodulation

Cancer vaccines inducing antibody production: more pros than cons

Developing strategies to enhance and focus humoral immune responses using filamentous phage as a model antigen

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