2022 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 | protein modelling / SARS-CoV-2 / influenza hemagglutinin |
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| Outline of Annual Research Achievements |
We were able to produce the molecular structure of one of the protein antigens that would be used throughout the study. More specifically, the SARS-CoV-2 spike protein from the original, alpha, beta, gamma, and delta variants were successfully designed in silico. We were able to publish our preliminary results related to the in silico design of the SARS-CoV-2 in a peer-reviewed journal. At present, we are likewise designing molecular structures related to the influenza A H3N2 and influenza B/Yamagata hemagglutinin (HA) proteins. Additionally, we also decided to add additional proteins for molecular structure design, namely: SARS-CoV-2 omicron spike and influenza A H5N1 HA proteins since the on-going pandemic is mainly associated with the omicron variant while the on-going bird flu epidemic might have the potential to cross to humans. Protein structures that have already been designed are currently undergoing epitope screening to identify potential B- and T-cell-related conformational epitopes associated with immune response. Moreover, we were also able to perform and confirm xanthan gel and antigen docking involving some of the SARS-CoV-2 spike proteins. We are currently confirming whether epitopes associated with activating B- and T-cell immune responses are readily exposed after xanthan gel molecule docking.
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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 one of our target antigen protein (SARS-CoV-2 spike protein) in silico. Multiple spike proteins related to the original, alpha, beta, gamma, and delta variants were made. Other antigen protein targets (influenza A H3N2 and B/Yamagata hemagglutinin) are currently being designed. In addition, the spike protein from the SARS-CoV-2 omicron variant and the hemagglutinin protein from the influenza A H5N1 are also being considered. Similarly, xanthan gel and antigen docking were likewise done and confirmed involving some of the SARS-CoV-2 spike proteins. We are currently confirming whether epitopes associated with activating B- and T-cell immune responses are readily exposed after xanthan gel molecule docking. Two papers were successfully accepted for publication in two different peer-reviewed journals.
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| Strategy for Future Research Activity |
Commercially available SARS-CoV-2 spike, influenza A H3N2 HA, and influenza B HA at varying concentrations will be used for antigen:gel ratio optimization. Industrial-grade xanthum gum will be used as the gel component. Varying mixing options will be considered in order to establish the optimal antigen:gel ratios for all three target antigens. Additionally, optimization for liquid vaccination mixture for use in alternative vaccination strategies (sublingual, oral, intramuscular) and direct gingival injection will likewise be performed.
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| Causes of Carryover |
Savings from the previous year is due to the reduction in price of several of the materials needed which include the SARS-CoV-2 protein antigen. Industrial-grade xanthum gum will be purchased and used as the gel component. For the subsequent year, varying mixing options will be considered in order to establish the optimal antigen:gel ratios for all target antigens.
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