2016 Fiscal Year Research-status Report
高齢者における歯肉溝経由ワクチン接種法の開発とその応用
| Project/Area Number |
16K11525
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| Research Institution | Nihon University |
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Principal Investigator |
Cueno Marni 日本大学, 歯学部, 専修研究員 (20569967)
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| Co-Investigator(Kenkyū-buntansha) |
落合 智子 (栗田智子) 日本大学, 松戸歯学部, 教授 (20130594)
落合 邦康 日本大学, 歯学部, 特任教授 (50095444)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | vaccine design / oral vaccination |
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| Outline of Annual Research Achievements |
Objectives: (1) To design a gel-encapsulated gingival vaccine in silico; (2) to determine Langerhan cells (LC) within the sulcular epithelium; and (3) to optimize the vaccine conditions for the other vaccination routes (nasal and sublingual). Methods: For vaccine design, special computer software was used in order to structurally visualize our proposed trivalent gingival vaccine. For LC determination, we utilized both a histological (staining) and biochemical (FceRIg) approach to estimate LC number. For optimization of other vaccination routes, ideal experimental animal (rat or mouse) and appropriate antigen concentration to induce an antibody response are both performed. Results: For vaccine design, in silico determination of gel-encapsulated antigens [H1N1 nucleoprotein, H5N1 hemagglutinin, dengue envelope-2 protein] were established. Gel encapsulation seems to suggest that all antibody epitopes for each of the antigens are unblocked. This would insinuate that an antibody response can be induced. For LC determination, there was difficulty establishing the LC number along the sulcular epithelium using a histological approach. An ELISA system targeting a common LC marker (FceRIg) was used instead since FceRIg levels would correlate to LC number. For optimization of other vaccination routes, conditions for sublingual vaccination route have been optimized. Optimization for the nasal vaccination route is still ongoing.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
We were able to follow the scheduled plan as indicated in our earlier proposal. For vaccine design, in silico determination of gel-encapsulated antigens were fully made. For LC determination, although there was difficulty establishing the LC number along the sulcular epithelium using a histological approach, using an ELISA system was found effective. For optimization of other vaccination routes, conditions for sublingual vaccination route was optimized while optimization for the nasal vaccination route is still ongoing.
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| Strategy for Future Research Activity |
Objectives: To optimize the antigen:xanthan gel ratio components based on our earlier computer analyses; (2) to quantify the number of adaptive lymphocytes prior to vaccination; and (3) to optimize other possible vaccination routes.
Methods: For optimizing the antigen:xanthan gel ratio components, ideal antigen and xanthan gel concentrations in combination together will be determined. For quantifying adaptive lymphocyte number, FceRIg levels and another possible biochemical marker will be used and quantified using ELISA. For optimizing other possible vaccination routes (oral, intradermal), selected antigens from the current year [H1N1 nucleoprotein, H5N1 hemagglutinin, dengue envelope-2 protein] will be administered orally and intradermally to a selected experimental animal.
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| Causes of Carryover |
Shifting to a biochemical approach from a histological approach in order to determine Langerhan Cell (LC) number in the rat sulcular epithelium made LC estimation more accurate. This allowed us to save on time while maintaining efficiency.
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| Expenditure Plan for Carryover Budget |
The budget for the current fiscal year plus the money we obtained from the previous year will be used for optimizing the antigen:xanthan gel component ratio, determine the adaptive lymphocyte number through biochemical markers, and to optimize other possible vaccination routes.
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