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Immunogenicity of M13 phage vaccine displaying N-terminal region of amyloid beta peptide: comparison of M13 phage vaccine expressed as g3p fusion and g8p fusion

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Immunogenicity of M13 phage vaccine displaying

N-terminal region of amyloid beta peptide:

comparison of M13 phage vaccine expressed as

g3p fusion and g8p fusion

著者

MIYAHARA Ryuji, SHIMOTSU Akiko, MATSUSHITA

Yui, SHINOZAKI Taisuke, TSUKADA Mai, HASHIMOTO

Masahito, SUGIMURA Kazuhisa, HASHIGUCHI Shuhei

journal or

publication title

The Research Reports of the Faculty of

Engineering, Kagoshima University

volume

59

page range

25-25

year

2017-12

(2)

The International Congress of Immunology 2016, August 21-26, 2016, Melbourne

Immunogenicity of M13 phage vaccine displaying N-terminal region of amyloid

beta peptide: comparison of M13 phage vaccine expressed as g3p fusion and g8p

fusion.

Ryuji Miyahara

1

, Akiko Shimotsu

1

, Yui Matsushita

1

, Taisuke Shinozaki

1

, Mai Tsukada

1

, Masahito

Hashimoto

1

, Kazuhisa Sugimura

2

, Shuhei Hashiguchi

1

Abstract

Antibodies against amyloid-ß peptide (Aß) can reduce amyloid deposits and are considered as a potential therapeutic approach for Alzheimer's disease1,2. We have recently shown that M13 phage stimulate an innate immune response and induce a strong primary IgG response in mice without any inflammatory adjuvant materials3,4. Even a single immunization with 1011 pfu of phage induced a long-lasting antibody response. To investigate the potential of M13 phage as a vaccine carrier for Aß peptide, the sequences of 1-15 region of Aß were genetically linked to the N-terminus of M13 gene 3 protein or gene 8 protein, that correspond to Aß-g3p phage and Aß-g8p phage, respectively. When C57BL/6 mice were immunized subcutaneously with 1011 pfu of Aß-g3p phage in PBS solution, anti-Aβ IgG response was induced in two weeks after the secondary immunization. In the case of Aβ-g8p phage, anti-Aß IgG response was induced during a primary response. Anti-Aß antibody titer was comparable in the two mice groups. We also observed that Aβ-g8p phage induced IgG class switch in athymic (nu/nu) BALB/c mice, indicating that there are different immunological mechanisms of phage vaccine between g3p fusion and g8p fusion. Considering safety and habitual presence of an M13 phage, Aß1-15-displaying M13 phage may be promising as a safe AD vaccine.

References

1) Schenk D, et al. Nature, 400, 173-177, (1999). 2) Bard F, et al. Nat Med, 6, 916-919, (2000).

3) Hashiguchi S, et al. Biochem Biophys Res Commun,402, 19-22, (2010). 4) Tanaka K, et al, J.Neuroimmunol, 236, 27-38, (2011).

1

Graduate School of Science and Engineering, Kagoshima University, Kagoshima, Japan 2

Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan

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