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Development of Nonaggregating Poly-A Tailed Immunostimulatory AD Type CpG Oligodeoxynucleotides Applicable for Clinical Use
Joint Authors
Kuroda, Etsushi
Mochizuki, Shinichi
Sakurai, Kazuo
Aoshi, Taiki
Haseda, Yasunari
Kobiyama, Kouji
Narita, Hirotaka
Sato, Hideaki
Nankai, Hirokazu
Katakai, Yuko
Coban, Cevayir
Yasutomi, Yasuhiro
Ishii, Ken J.
Source
Journal of Immunology Research
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-20, 20 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-08-25
Country of Publication
Egypt
No. of Pages
20
Main Subjects
Abstract EN
Immunostimulatory CpG ODNs have been developed and utilized as TLR9-dependent innate immune activators and vaccine adjuvants.
Four different types of immunostimulatory CpG ODNs (A/D, B/K, C, and P type) have been reported.
A/D type ODNs are characterized by high IFN-α production but intrinsically form aggregates, hindering its good manufacturing practice grade preparation.
In this study, we developed several D35-derived ODNs (a commonly used A/D type ODN), which were modified with the addition of a phosphorothioate polynucleotide tail (such as dAs40), and examined their physical properties, solubility in saline, immunostimulatory activity on human PBMCs, and vaccine adjuvant potential in monkeys.
We found that two modified ODNs including D35-dAs40 and D35core-dAs40 were immunostimulatory, similar to original D35 in human PBMCs, resulting in high IFN-α secretion in a dose-dependent manner.
Physical property analysis by dynamic light scattering revealed that both D35-dAs40 and D35core-dAs40 did not form aggregates in saline, which is currently impossible for the original D35.
Furthermore, D35-dAs40 and D35core-dAs40 worked as better vaccine adjuvant in monkeys.
These results suggested that D35-dAs40 and D35core-dAs40 are two promising prototypes of nonaggregating A/D type ODN with advantages of ease of drug preparation for clinical applications as vaccine adjuvants or IFN-α inducing immunomodifiers.
American Psychological Association (APA)
Aoshi, Taiki& Haseda, Yasunari& Kobiyama, Kouji& Narita, Hirotaka& Sato, Hideaki& Nankai, Hirokazu…[et al.]. 2015. Development of Nonaggregating Poly-A Tailed Immunostimulatory AD Type CpG Oligodeoxynucleotides Applicable for Clinical Use. Journal of Immunology Research،Vol. 2015, no. 2015, pp.1-20.
https://search.emarefa.net/detail/BIM-1068438
Modern Language Association (MLA)
Aoshi, Taiki…[et al.]. Development of Nonaggregating Poly-A Tailed Immunostimulatory AD Type CpG Oligodeoxynucleotides Applicable for Clinical Use. Journal of Immunology Research No. 2015 (2015), pp.1-20.
https://search.emarefa.net/detail/BIM-1068438
American Medical Association (AMA)
Aoshi, Taiki& Haseda, Yasunari& Kobiyama, Kouji& Narita, Hirotaka& Sato, Hideaki& Nankai, Hirokazu…[et al.]. Development of Nonaggregating Poly-A Tailed Immunostimulatory AD Type CpG Oligodeoxynucleotides Applicable for Clinical Use. Journal of Immunology Research. 2015. Vol. 2015, no. 2015, pp.1-20.
https://search.emarefa.net/detail/BIM-1068438
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1068438