Malaria endemic countries (WHO 2009)
Urgent need for the malaria vaccine development
The disease “Malaria” is responsible for approximately one million deaths annually, mostly African children under the age five, and 300 million clinical cases every year, resulting in an enormous public health burden on many of the tropical and subtropical countries. Moreover, the burden due to malaria keeps increasing because of the spread of drug resistant parasites and insecticide resistant mosquito vectors. Therefore, there is an urgent need for the discovery of new malaria vaccines and drugs. We should also keep in mind the fact that, until now, not even a single licensed malaria vaccine has been developed despite intensive efforts.
Hurdle for the post-genome malaria vaccine development
The genome sequence of Plasmodium falciparum became available, since 2002, for the purpose of discovering cure for malaria. To find novel malaria vaccine candidates, we need to synthesize, screen, and characterize quality malarial proteins. However, conventional recombinant protein expression methods, such as E. coli based system, are inefficient in expressing highly AT-rich malaria genes into quality proteins.
Wheat germ cell-free system clears the hurdle
To overcome the above mentioned hurdle, we employed a cell-free protein expression system prepared from wheat embryos. Our biochemical, immunocytochemical, and biological analyses have revealed that the recombinant malaria proteins synthesized by this system are of high quality and therefore amenable for the assessment and discovery of potential vaccine targets. From a malaria vaccine perspective, wheat germ cell-free system is the most suitable system to date for easily achieving high-throughput, high-solubility, and high-productivity in the whole-proteome-scale synthesis of malaria proteins.
Post-genome immunoscreening approach for identification of novel vaccine candidates
We synthesized microarrays of malaria proteins for accelerating post-genomic novel malaria vaccine candidate discovery. Initially putative vaccine candidates were selected based on their immuno-reactivity with the protective antibodies that are elicited in humans, after natural infection. For our immuno-reactivity studies, we obtained human serum samples from Asian and African malaria endemic populations. Based on the preliminary screening, we have already identified novel immunoreactive parasite antigens.
Functional analyses of the vaccine candidate molecules are essential for understanding
the mode of action of the vaccine
We immunized experimental animals by the selected recombinant parasite proteins expressed using wheat germ cell-free system. The antibodies thus raised are being used in our parasite growth inhibition assay to assess the vaccine efficacy. Moreover, we endeavor to analyze the function of the parasite antigens during the course of parasite invasion into the host cell.
These methods and approaches have opened promising avenues for the identifying novel malaria vaccine candidates with clear functional understandings.
Professor: Takafumi Tsuboi, MD, PhD (firstname.lastname@example.org)
Associate professor: Eizo Takashima, PhD (takashima.eizo.mz@ehime-u-.ac.jp)