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Development of the World’s First Monoclonal IgE Antibody for Schistosomiasis

Affecting more than 200 million people worldwide, the impact of schistosmiasis as an infectious disease is second only to malaria. Soumei Kojima is the first in the world to succeed in creating a monoclonal immunoglobulin E (IgE) antibody that responds to the vaccine candidate molecule.

Experiences in Taiwan lead to blood fluke research

First Japan–Taiwan Christian Medical Association joint visit to villages without doctors (Guangfu, Hualien, Taiwan, 1963)

Kojima first encountered parasitology in the summer of 1963, during his third year of medical school. He was participating in a project offering medical examinations in mountainous areas of Taiwan, where there were no doctors, and was surprised by the number of people infected by parasites. “In the coming era it will not be viruses or bacteria but parasites that will be most important for us to contend with,” he thought, and thus decided to pursue a path in parasitology. His rebellious spirit urged him to “do the work no one else wants to,” giving him a sense of duty and purpose in exploring this field where few others ventured.

The story of the discovery of schistosomiasis japonicum in the Edo Period

In the late Edo Period (1603-1868), a strange disease plagued areas such as the Katayama district of Hiroshima, the Kofu Basin of Yamanashi, and the Chikugo River basin of Kyushu. After working in the fields, people developed rashes, fever, and abdominal swelling, finally leading to intestinal bleeding, weight loss, and even death.

In 1904, separately and unaware of each other’s efforts, two doctors, Fujirou Katsurada and Akira Fujinami, began tests to understand the disease. On May 26, Katsurada determined that a parasite was the cause of the sicknesses in Yamanashi, and in August, he published a paper in which he gave it the name Schistosoma aponicum. Fujinami saw the paper and was shocked—he had also detected the parasite in Hiroshima a mere four days after Katsurada. Though mention of an author’s emotions in scientific publications is unusual, Fujinami expressed his surprise in the paper, writing that he “could hear footsteps in the valley,” a phrase referring to the feeling of receiving unexpected news when alone. At the same time, in Kyushu, a doctor named Keinosuke Miyairi was investigating field side ditches, trying to find the source of rashes appearing the lower legs of people who worked in the rice fields. He discovered the role of snails, proving that they were the intermediary host for the blood flukes in their larval stage. These snails were named “Miyairi snails” after him.

Even more surprising is the connection that all three of these Japanese men, Katsurada, Fujinami and Miyairi, had to a doctor named Erwin Bälz, who came to Japan from Germany in 1876. Bälz had a major impact on parasitology, and Fujinami and Miyairi were among his many students. Even Touichirou Nakahama (the son of John Manjirō), who taught Katsurada, was a student of Bälz.

Kojima says, “The research of my great predecessors forms the foundations of parasitology.”

Success in manufacturing the world’s first antibody for schistosomiasis

ニューヨーク大学留学中の様子の画像

Kojima (second from the back left) in a pathology class with Professor Zoldan Ovary during his study abroad (1972–1974) in the medical school of New York University

Though drugs to treat schistosomiasis do exist, there is no vaccine. Kojima is focusing on the IgE antibody in his development of a vaccine. IgE is a type of immunoglobulin from which IgE antibodies that respond to the parasite after infection can be created.

Kojima has conducted his research over the years by studying abroad, both at New York University and through a short stay at Harvard University. In 1985, he succeeded in creating a monoclonal IgE antibody, the first in the world that responded to the blood fluke antigen and prevented infection in laboratory animals. Furthermore, he proved that the blood fluke’s paramyosin protein was the antibody’s target molecule and identified the arrangement of amino acids that bind to the antibody. He also showed the immunological mechanisms through which blood flukes with IgE proteins were attacked and killed by eosinophils (a type of white blood cell). In other words, he proved that the antigen paramyosin could be used in a vaccine.

Leading research from the United States did not consider paramyosin as a vaccine candidate molecule. However, because of Kojima’s research, WHO has added paramyosin to the list of vaccine-candidate molecules. Unfortunately, there has not yet been sufficient research regarding its application and effectiveness on humans, and the development of a vaccine remains a long way off. Acknowledging his frustration while maintaining high hopes for future research on vaccines, Kojima says:

Research on proteins and genes is needed to create a vaccine. I have no choice but to leave that to the younger generation. There is currently only one drug for treatment. We need to develop new medicines and use treatment and vaccines in conjunction to prevent reinfection.

“Look at the world” to infuse research with meaning

The development of vaccines and medical treatment must be conducted with patients in mind. However, working in a region unaffected by the disease can make it difficult to see the significance of such work. Speaking of the driving force behind his research, Kojima says, “Look at the world and see what people are suffering from, and then bring what you see and feel to life in your research.” He added, “When performing cutting-edge research, you must see it through to the end, all the way to practical implementation.” Furthermore, he goes on to say:

Think about our lives and all the electronic products we have. We do not know anything about the structure of a television, yet with a single button, we can enjoy the benefits of the science behind it. The technical details are taken care of in a research laboratory, which involves not only creating it but also ensuring that people who know nothing of the mechanics behind it can use it properly: this is the true goal of science, to make sure that people can enjoy its benefits every day. I want the young people of this generation to be aware of this.

Neglected diseases, such as malaria and schistosomiasis, are common in the most impoverished parts of the world today. Many in developed countries prioritize economic development matters and ignore diseases of the poor.

Kojima wants people to endeavor to “shine light on ignored diseases so that poor people can become healthy, and once healthy can contribute to society.

Note: Quotes are from a June 12, 2015, interview with Soumei Kojima.

Research on Schistosomiasis

Soumei Kojima

Soumei Kojima was born in Tokyo in 1940 and received his PhD from the Chiba University School of Medicine. He has devoted his career to developing a vaccine for schistosomiasis. Ever since Prime Minister Ryutaro Hashimoto proposed efforts to combat parasites in 1997, Kojima has been involved in the creation of various projects to deal with tropical diseases around the world. He is professor emeritus at Tokyo University.

Image of Soumei Kojima

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