Research

Research Theme

The Project Leader's Profile

Toshihiro Horii

Professor, Department of Molecular Protozoology

Project Leader
  • Toshihiro Horii, Ph.D., Professor
Research Members
  • Taiki Aoshi, COE Assistant professor
Research Collaborators
  • Ken Ishii, Associate professor
  • Nobuko Arisue, Assistant professor
  • Takahiro Tougan, Assistant professor
  • Masanori Yagi, Research Fellow

Summary

Malaria is a serious threat to global human health. More than 40% of the world's population lives in malaria-endemic areas and two million people succumb to the disease annually. Controlling malaria has become more challenging since the emergence of drug-resistant malaria parasites. This has increased the urgency for the development of a practical vaccine and novel anti-malarial drugs. The research in our department focuses on the development of malaria vaccine and anti-malarial drugs. We are also working towards understanding the strategies used by the malaria parasite to survive in the host.

(1) Development of a recombinant vaccine based on the malaria protein SERA
We are developing a malaria vaccine using SE36, a recombinant protein which based on an amino acid sequence present in the serine repeat antigen (SERA) of malaria parasites. We and co-researchers in malaria-endemic areas have demonstrated that naturally acquired immunity against malaria is exclusively correlated with the development of anti-SERA IgG3 antibodies. We also showed that many types of animals, including chimpanzees, develop antibodies upon vaccination with SE36 that inhibit the growth of malaria parasites. Collaborating with the Kan-onji Institute of The Research Foundation for Microbial Diseases of Osaka University, we have constructed a system by which the SE36 malaria vaccine can be mass produced. We have conducted a phase I clinical trial in Japan in 2005 with SE36 to assess its safety and immunogenicity. Among vaccine administered volunteers, we found 100% of sero-conversion without any serious adverse effects. We have planned further clinical trials in endemic regions including Africa. This project has been conducted by the collaboration of our laboratory with The Research Foundation for Microbial Diseases of Osaka University and WHO-TDR.
We are also studying a function of SERA molecule in the parasite and the host immune response against SERA. In addition, we have started a new research project for P. vivax vaccine development by collaborating with colleagues in Uganda, Thai, Indonesia and Solomon.
(2) Development of a novel vaccine adjuvant and elucidation of its mechanism of action
In order to improve efficacy of vaccines that are currently in use or under clinical development, including SE36 vaccine, we take multiple approaches including the development of a novel vaccine adjuvant. In addition, its mechanism(s) of action such as functions of antigen presenting cells and its innate and adaptive immune activation cascades.

Some of Recent Papers

  1. Hayakawa, T., Culleton, R., Otani, H., Horii, T., and Tanabe, K. Big bang in the evolution of extant malaria parasites. Molecular Biology and Evolution 25, 2233-2239, 2008.
  2. Coban, C., Ishii, K.J., Horii, T., and Akira, S. Manipulation of host innate immune responses by the malaria parasite. Trends in Microbiology 15, 271-278, 2007.
  3. Arisue, N., Hirai, M., Arai, M., Matsuoka, H., and Horii, T. Phylogeny and evolution of the SERA multigene family in the genus Plasmodium. Journal of Molecular Evolution 65, 82-91, 2007.
  4. Palacpac, N.M., Leung, B.W., Arisue, N., Tanabe, K., Sattabongkot, J., Tsuboi, T., Torii, M., Udomsangpetch, R., and Horii, T. Plasmodium vivax serine repeat antigen (SERA) multigene family exhibits similar expression patterns in independent infections. Molecular and biochemical parasitology 150, 353-358, 2006.
  5. Coban, C., Ishii, K.J., Kawai, T., Hemmi, H., Sato, S., Uematsu, S., Yamamoto, M., Takeuchi, O., Itagaki, S., Kumar, N., Horii, T., and Akira, S. Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin. Journal of Experimental Medicine 201, 19-25, 2005.