Development of Nonaggregating Poly-A Tailed Immunostimulatory A/D Type CpG Oligodeoxynucleotides Applicable for Clinical Use
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 fo...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2015/316364 |
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| author | Taiki Aoshi Yasunari Haseda Kouji Kobiyama Hirotaka Narita Hideaki Sato Hirokazu Nankai Shinichi Mochizuki Kazuo Sakurai Yuko Katakai Yasuhiro Yasutomi Etsushi Kuroda Cevayir Coban Ken J. Ishii |
| author_facet | Taiki Aoshi Yasunari Haseda Kouji Kobiyama Hirotaka Narita Hideaki Sato Hirokazu Nankai Shinichi Mochizuki Kazuo Sakurai Yuko Katakai Yasuhiro Yasutomi Etsushi Kuroda Cevayir Coban Ken J. Ishii |
| author_sort | Taiki Aoshi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-361f12e4e542406098cf68c631a72e42 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-361f12e4e542406098cf68c631a72e422025-08-20T03:55:07ZengWileyJournal of Immunology Research2314-88612314-71562015-01-01201510.1155/2015/316364316364Development of Nonaggregating Poly-A Tailed Immunostimulatory A/D Type CpG Oligodeoxynucleotides Applicable for Clinical UseTaiki Aoshi0Yasunari Haseda1Kouji Kobiyama2Hirotaka Narita3Hideaki Sato4Hirokazu Nankai5Shinichi Mochizuki6Kazuo Sakurai7Yuko Katakai8Yasuhiro Yasutomi9Etsushi Kuroda10Cevayir Coban11Ken J. Ishii12Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka 567-0085, JapanLaboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka 567-0085, JapanLaboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka 567-0085, JapanLaboratory of Supramolecular Crystallography, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, JapanGeneDesign Inc., Ibaraki, Osaka 567-0085, JapanGeneDesign Inc., Ibaraki, Osaka 567-0085, JapanDepartment of Chemistry and Biochemistry, University of Kitakyushu, Kitakyushu, Fukuoka 808-0135, JapanDepartment of Chemistry and Biochemistry, University of Kitakyushu, Kitakyushu, Fukuoka 808-0135, JapanCorporation for Production and Research of Laboratory Primates, Tsukuba, Ibaraki 305-0843, JapanTsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki 305-0843, JapanLaboratory of Vaccine Science, Immunology Frontier Research Center (iFReC), Osaka University, Suita, Osaka 565-0871, JapanLaboratory of Malaria Immunology, Immunology Frontier Research Center (iFReC), Osaka University, Suita, Osaka 565-0871, JapanLaboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka 567-0085, JapanImmunostimulatory 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.http://dx.doi.org/10.1155/2015/316364 |
| spellingShingle | Taiki Aoshi Yasunari Haseda Kouji Kobiyama Hirotaka Narita Hideaki Sato Hirokazu Nankai Shinichi Mochizuki Kazuo Sakurai Yuko Katakai Yasuhiro Yasutomi Etsushi Kuroda Cevayir Coban Ken J. Ishii Development of Nonaggregating Poly-A Tailed Immunostimulatory A/D Type CpG Oligodeoxynucleotides Applicable for Clinical Use Journal of Immunology Research |
| title | Development of Nonaggregating Poly-A Tailed Immunostimulatory A/D Type CpG Oligodeoxynucleotides Applicable for Clinical Use |
| title_full | Development of Nonaggregating Poly-A Tailed Immunostimulatory A/D Type CpG Oligodeoxynucleotides Applicable for Clinical Use |
| title_fullStr | Development of Nonaggregating Poly-A Tailed Immunostimulatory A/D Type CpG Oligodeoxynucleotides Applicable for Clinical Use |
| title_full_unstemmed | Development of Nonaggregating Poly-A Tailed Immunostimulatory A/D Type CpG Oligodeoxynucleotides Applicable for Clinical Use |
| title_short | Development of Nonaggregating Poly-A Tailed Immunostimulatory A/D Type CpG Oligodeoxynucleotides Applicable for Clinical Use |
| title_sort | development of nonaggregating poly a tailed immunostimulatory a d type cpg oligodeoxynucleotides applicable for clinical use |
| url | http://dx.doi.org/10.1155/2015/316364 |
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