Reverse toxicology for identifying novel, safe, and effective vaccine adjuvants

DOI
  • MIZUKAMI Takuo
    Department of Safety Research on Blood and Biologicals, National Institute of Infectious Diseases
  • MOMOSE Haruka
    Department of Safety Research on Blood and Biologicals, National Institute of Infectious Diseases
  • SASAKI Eita
    Department of Safety Research on Blood and Biologicals, National Institute of Infectious Diseases
  • FURUHATA Keiko
    Department of Safety Research on Blood and Biologicals, National Institute of Infectious Diseases
  • KUSUNOKI Hideki
    Department of Safety Research on Blood and Biologicals, National Institute of Infectious Diseases
  • ASANUMA Hideki
    Influenza Research Center, National Institute of Infectious Diseases
  • HAMAGUCHI Isao
    Department of Safety Research on Blood and Biologicals, National Institute of Infectious Diseases

Bibliographic Information

Other Title
  • Reverse toxicologyによる新規アジュバント・スクリーニング系の開発

Abstract

<p> For the control of emerging infectious diseases, rapid vaccine development is often needed. However, owing to the low immunogenicity of antigens, vaccine adjuvants with high safety and efficacy profiles are needed to induce complete immune responses to vaccines. Although aluminum adjuvants have been widely used in different types of vaccines and they ensure efficacy and safety, the development of a mode of action (MOA)-based adjuvant is desired.</p><p> Our group revealed the MOA of influenza vaccine with different types of adjuvants and identified influenza vaccine-specific biomarkers (BMs) that correlate immune response and toxicity, including antibody production, cytokine production, and hematological toxicity. Using these BMs, we established a new method for evaluating the safety and efficacy of influenza vaccine as well as adjuvants. In the present study, we applied a reverse toxicology to identify novel, safe, and effective adjuvants based on the expression of our BMs both in vitro and in vivo. We established an in vitro screening method to determine the BM levels after interaction of different adjuvant candidates with influenza HA antigen and compare the BM levels in response to HA antigen itself. The adjuvanticity of the candidates was determined using these results, and whole inactivated influenza vaccine was used as a toxicity reference for determining the safety of adjuvants. Using our method, we identified a novel adjuvant candidate with a high safety and efficacy profile. In conclusion, our reverse toxicological approach can enable the identification of novel, safe, and effective adjuvants. </p>

Journal

Details 詳細情報について

  • CRID
    1390004222614678528
  • NII Article ID
    130007898151
  • DOI
    10.14869/toxpt.47.1.0_o-15
  • Text Lang
    ja
  • Data Source
    • JaLC
    • CiNii Articles
  • Abstract License Flag
    Disallowed

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