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2019 Fiscal Year Research-status Report

Gel vaccine designed to co-stimulate both humoral and cellular immunity ideal for elderly vaccination

Research Project

Project/Area Number 19K10097
Research InstitutionNihon University

Principal Investigator

Cueno Marni  日本大学, 歯学部, 専修研究員 (20569967)

Project Period (FY) 2019-04-01 – 2022-03-31
Keywordsinfluenza A / influenza B / gingival vaccine
Outline of Annual Research Achievements

We were able to produce the molecular structures of the different protein antigens that would be used throughout the study. More specifically, both influenza A H3N2 and B/Yamagata hemagglutinins were successfully designed in silico and, more importantly, are commercially available. We were able to publish our preliminary results related to the in silico design of the influenza B/Yamagata hemagglutinin in a peer-reviewed journal. At present, both protein antigens were already purchased and now available for use in the succeeding year. Similarly, the chosen pneumonia protein antigen (pneumolysin) was successfully design, however, high amounts of pneumolysin is no longer commercially available which is why an alternative pneumonia protein antigen is currently being searched and, subsequetly, designed. Additionally, identifying biochemical networks ideal for assessing CNS demyelination has been established. Considering the complex biochemical networks involved in CNS deamylation, network analysis (using Cytoscape) will be performed was all known biochemical networks are identified. Holistic analyses will be done through centrality measurements in order to identified specific biocehmical components involved.

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 our target antigen proteins (influenza A and B) in silico. A third protein antigen targeting pneumonia is currently being designed. Moreover, xanthan gel and antigen docking were likewise successfully done. In additiona, we would have established the following: (1) potential B- and T-cell-related epitopes that are exposed after gel-encapsulating target antigens are mainly located in tha HA1 region; (2) optimized conditions for systemic vaccination strategies which in-turn will be used as control; and (3) biochemical networks ideal for assessing CNS demyelination are established, but further analyses is being done using centrality measurements. First year objectives were successfully fulfilled and a paper was successfully accepted for publication in a peer-reviewed journal.

Strategy for Future Research Activity

Commercially available 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 target antigens.

Causes of Carryover

Savings from the previous year is due to the unavailability of the pneumolysin protein antigen. Nevertheless, commercially available influenza A H3N2 and influenza B/Yamagata HA at high amounts were purchased and will be used for antigen:gel ratio optimization. Industrial-grade xanthum gum is available and will be 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. Additionally, sublingual vaccination conditions will be optimized and the proposed CNS demyelination standard through in vitro and in vivo experimentations will be evaluated.

  • Research Products

    (2 results)

All 2020 2019

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Structural insights into the potential changes in receptor binding site found in the influenza B Yamagata hemagglutinin: A putative correlation between receptor binding site structural variability and seasonal infection2020

    • Author(s)
      Marni E.Cueno, Kanako Iguchi, Kanta Suemitsu, Marina Hirano, Kosei Hanzawa, Takemasa Isoda, Miu Ueno, Rinako Iguchi, Aoi Otani, Kenichi Imai
    • Journal Title

      Journal of Molecular Graphics and Modelling

      Volume: 97 Pages: 107580

    • DOI

      10.1016/j.jmgm.2020.107580

    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Structural variations in the influenza B hemagglutinin receptor binding site coincide with viral evolution and infection: A computational study with antiviral applications2019

    • Author(s)
      Marni E. Cueno, Kenichi Imai
    • Organizer
      27th Intelligent Systems for Molecular Biology and 18th European Conference on Computational Biology
    • Int'l Joint Research

URL: 

Published: 2021-01-27  

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