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 (Fig.1). Controlling malaria has become more challenging since the emergence of drug-resistant malaria parasites. This has intensified the need for novel drug target strategies and an effective malaria vaccine. Our department is focused on the development of both anti-malarial vaccines and drugs. We are also seeking to understand the mechanisms that the malaria parasite uses to survive in the host.
(1) Development of a recombinant vaccine based on the malaria protein SERA.
We are developing a malaria vaccine that is based on SE36, which is a recombinant protein that spans an amino acid sequence in the serine repeat antigen (SERA) of malaria parasites (Fig. 2). We and co-researchers in malaria-endemic areas have demonstrated that naturally acquired immunity against malaria correlates exclusively with the development of anti-SERA IgG3 antibodies. We have also shown that, after vaccination with SE36, many types of animals, including chimpanzees, develop antibodies that inhibit the growth of malaria parasites (Fig. 3). Together with the Kanonji Institute of the Research Foundation of Osaka University, we have constructed a system by which the SE36 malaria vaccine can be mass-produced (Fig. 4). In 2005, we conducted a phase I clinical trial in Japan with SE36 to assess its safety and immunogenicity. All vaccine-administered volunteers were sero-converted and showed no serious adverse events. We are currently in the process of conducting additional phase Ib clinical trials in an endemic region in Uganda. This project is under taken in collaboration with the Research Foundation for Microbial Diseases of Osaka University
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We are also studying the function of the SERA molecule in the parasite and characterizing the host immune response against SERA. In addition, in collaboration with colleagues in Uganda, Thailand, Indonesia and the Solomon Islands, we have started a new research project that aims to develop a Plasmodium vivax vaccine.
Fig. 1: Patients waiting at the Out-patient Department of Apac Hospital in Northern Uganda: major victims of malaria are children under the age of 5 years. |
Fig. 2: Processed fragments of P. falciparum SERA and the structure of the recombinant SE36. |
Fig. 3: Model that explains how anti-SERA IgG inhibits erythrocytic P. falciparum growth. |
Fig. 4: The SE36 malaria vaccine for clinical trials is produced under Good Manufacturing Practices (GMP) at the Kanonji Institute of the Research Foundation for Microbial Diseases of Osaka University. |
(2) Identification of SERA genes from several Plasmodium species.
The Plasmodium SERA gene family consists of several gene members. To trace the evolution of the SERA genes, we identified the SERA genes of several Plasmodium species and constructed the SERA gene family tree (Fig. 5). Transcription and polymorphic analyses are being used to search for functional or vaccine target molecules in the Plasmodium SERA genes.
Fig. 5:ĦĦAn overview of the Plasmodium SERA gene family.