Development of sublingual mucosal vaccine adjuvant for neonates and infants
Project/Area Number |
16K10039
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Pediatrics
|
Research Institution | Osaka City University |
Principal Investigator |
|
Research Collaborator |
HIKITA norikatsu
TACHIBANA daisuke
CHO yuki
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | ワクチン / アジュバント / 感染症 / 小児 / 臍帯血 / 自然免疫 / Toll様受容体 / zymosan / ノロウイルス / 免疫学 |
Outline of Final Research Achievements |
Human cord blood and adult peripheral blood monocytes were isolated and stimulated with lipopolysaccharide (TLR4 agonist) or zymosan (TLR2/6 agonist). Expression levels of MHC-class II, CD80, CD86, CD11b, CD11c, CD14, and CD16 were evaluated. Cord blood CD14+CD16high monocytes showed significantly lower levels of basal expression of MHC-class II, CD80, and CD11b compared with those of adult CD14+CD16intermediate monocytes. The ratios of lipopolysaccharide-stimulated expression levels to basal levels for MHC-class II, CD80, and CD11b and the ratios of zymosan-stimulated expression levels to basal levels for MHC-class II, CD86, CD11b, and CD11c were significantly higher in cord blood monocytes than in adult blood monocytes. Despite showing selective impairment of basal expression of surface antigens, neonatal monocytes are hyperresponsive to TLR stimulation compared with adult. Application of TLR agonists may complement induction of protective immunity as a vaccine adjuvant in children.
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Academic Significance and Societal Importance of the Research Achievements |
現在のワクチンは健常成人や成熟マウスにおける効果をもとに開発され、乳幼児に応用されている。しかし乳幼児はそれらのワクチンによる免疫誘導効果が低く、成人よりも複数回の接種を必要とする。その問題点を克服するためには、成熟した免疫システムを対象にしたワクチンの開発ステップを見直す必要があり、乳幼児免疫の理解に立脚したワクチン開発が望ましい。しかし、乳幼児から研究用に血液を採取することは侵襲性が高いため、我々は痛みを伴わずに採取できる臍帯血を用いた解析を展開している。本研究成果はヒト臍帯血から得られるため、動物実験や成人で得られた結果よりもシームレスに乳幼児に特化したワクチン開発への応用が期待できる。
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Report
(4 results)
Research Products
(5 results)