Development of DNA vaccine for Clostridium difficile infection

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19132
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Bacteriology (including mycology)
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Senoh Mitsutoshi 国立感染症研究所, 細菌第二部, 主任研究官 (20646624)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: Clostridium difficile / Clostridioides difficile / CDI / DNAワクチン

Outline of Final Research Achievements

Clostridioides (Clostridium) difficile infection (CDI) is a global health concern because of the high recurrence rate after standard antibiotic therapy. As serious intestinal conditions occur by C. difficile toxins, we considered measures about inactivation of toxins. Vaccination is one of prevention measures by which low recurrence rate is expected. In this study, DNA vaccine for C. difficile toxin B devoid of toxic active site was synthesized and inserted to pVAX1 to construct DNA vaccine. DNA vaccine thus prepared was transfected to HEK293T cells, and the expression of the target proteins were confirmed by western blot. Immunized mice by DNA vaccine produced anti-C. difficile toxin B antibodies and these antibodies neutralized cytotoxic activity of toxin B. Interestingly, immunized mice by DNA vaccine protected cytotoxic activity of toxin A in spite of DNA vaccine for toxin B. These results show the potential of DNA vaccine which constructed in this study as a vaccine for CDI.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

Clostridioides (Clostridium) difficile感染症(CDI)の新たな予防法として、毒素を標的としたDNAワクチンを構築した。毒素を標的としたワクチンはトキソイドが有名であるが、毒素活性の残存や復帰の可能性がある。しかし、本研究で構築したDNAワクチンは毒素の活性領域を完全に取り除いているため、トキソイドのような副反応は起こらない。さらに、本ワクチンはC. difficileの主要な毒素であるtoxin Bとtoxin Aのどちらにも効果があるため、非常に高い効果が期待される。よって、コントロールすることが難しいCDIに対する有用な手法の１つになると考えられる。