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P2–396: A novel method for enhancement of peptide vaccination utilizing T‐cell epitopes from conventional vaccines
Author(s) -
Kanazawa Yoshito,
Yano Akira,
Miwa Yoshikatsu,
ItoTakahashi Kaori,
Makino Mitsuhiro,
Imai Susumu,
Hanada Nobuhiro
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.05.1045
Subject(s) - epitope , toxoid , immunogenicity , peptide vaccine , antigen , peptide , diphtheria toxin , antigenicity , virology , immunization , medicine , booster dose , vaccination , tetanus , immunology , biology , microbiology and biotechnology , toxin , biochemistry
Background: A hallmark in the brains of patients with Alzheimer’s disease (AD) is the aggressive appearance of amyloid beta (Ab) aggregates causing progressive neuronal dysfunction. Anti-Ab immunization has been proposed as a potential therapeutic approach forAD.A previous clinical study indicated that active immunization (AN-1792) of patients with AD reduced the level of brain Ab deposition, although it was halted due to Th1 mediated meningoencephalitis, suggesting that safe immunotherapy is beneficial to the patients with AD. In this study, we determined the effect of a novel Ab peptide vaccine utilizing a conventional vaccination approaches inADmodelmice.Methods: Diphtheria and tetanus toxoids (DT, 50 m L/head, s.c.) were administered to Tg2576 mice. Twoweeks after the DT treatment, RGD-DiTox 382-401 -KKAb 1-13 peptide (50 m g/50 m L/head, i.p.) or vehicle in incomplete Freund’s adjuvant were administered to mice at intervals of 2 weeks (total 9 times i.p. administration). Plasmawas collected everyweek after the administration and anti-Ab antibody levels were measured by ELISA. A passive avoidance test was performed one week after the final treatment. Two weeks after the final treatment, the levels of Ab in brain, CSF and plasma were measured by ELISA. The proliferation rate of splenocytes and cytokine levels secreted from splenocytes induced by stimulating antigens were measured by ELISA. Results: Inmice treated with Ab peptide vaccine, the concentration of plasma antiAb antibodies increased. The brain Ab deposition decreased and the Ab levels in plasma and CSF increased in Ab peptide vaccine treated mice compared with the vehicle treated mice. Treatment with Ab peptide vaccine increased the latency in the passive avoidance test. A proliferation of splenocytes from Ab peptide vaccinated mice was promoted by stimulation with Ab peptide, and resulted in the production of Th2 type cytokines (IL4 and IL-10), but not Th1 type cytokines (IL-2, TNFa and IFNg).Conclusions: The results in this study suggested that RGD-DiTox 382-401 -KK-Ab 1-13 peptide vaccine in combination with a conventional vaccination promotedAb clearance through induction of Th2 type immune response.We propose that this peptide would be a possible therapeutic candidate for AD.