2023 Fiscal Year Research-status Report
Gingival vaccination strategy to induce both humoral and cellular immunity ideal for elderly vaccination
| Project/Area Number |
22K09932
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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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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Keywords | SARS-CoV-2 spike / influenza HA / gingival vaccination |
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| Outline of Annual Research Achievements |
We were able to design the molecular structures related to the following: SARS-CoV-2 spike protein, influenza A H3N2 hemagglutinin (HA) and H5N1 HA, and influenza B/Yamagata HA proteins. Additionally, we were also able to do in silico xanthan gel molecular docking and confirmed that protein epitopes associated with activating B- and T-cell immune responses are readily exposed after xanthan gel molecule docking. We were able to optimize the antigen:gel ratio for influenza A H3N2 HA, H5N1 HA, and influenza B/Yamagata HA while antigen:gel ratio optimization for SARS-CoV-2 spike proteins are on-going.
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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 successfully designed and produced all our desired target antigen proteins (SARS-CoV-2 alpha, beta, gamma, delta, omicron spike proteins, influenza A H3N2 HA, influenza A H5N1 HA, influenza B/Yamagata HA) in silico. Additionally, antigen:gel ratio optimization for influenza A H3N2 HA, influenza A H5N1 HA, influenza B/Yamagata HA were done while antigen:gel ratio optimization for SARS-CoV-2 alpha, beta, gamma, delta, and omicron spike proteins are on-going. Three manuscripts have been written and submitted to internationally peer-reviewed journals and are currently under review.
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| Strategy for Future Research Activity |
Vaccination of the optimized antigen:gel ratio along the gingival crevice will be performed. ELISA (B-cell immunity) and ELISPOT (T-cell immunity) will be performed following previously published work. Immune response from all all protein antigens (SARS-COV-2 spike, influenza A HA, and influenza B HA) will be checked to establish immune efficacy of the gel vaccine. In addition, results will be compared to direct gingival, sublingual, oral, and intramuscular vaccination strategies.
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| Causes of Carryover |
Savings from the previous year (2023) was attributable to a delay in optimizing the antigen:gel ratio for each of the antigens studied. In this regard, we opted to prioritize antigen proteins from influenza A H3N2, influenza A H5N1, influenza B/Yamagata. Varying mixing options were optimized for the optimal antigen:gel ratios of all influenza antigens. For 2024, the budget will be used to purchase the appropriate model rat to test the different antigen:gel ratio optimized using the HA proteins. Similarly, since we will also optimize the antigen:gel ratio for the different spike proteins from the varying SARS-CoV-2 variants, we will also purchase the antigen protein and test the antigen:gel ratio in the appropriate model rat.
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