Press Release

Development of polysaccharide-based carriers that enhance antibody production to target molecules

"Development of polysaccharide-based carriers that enhance antibody production to target molecules"
-To develop a vaccine with high antibody-producing ability-

Published: November 30, 2021


Vaccines using purified target proteins are excellent in that they can induce an immune response to a specific target molecule, but it is not easy to elicit a sufficient immune response. 
It has been clarified that the use of polysaccharide-based substances can significantly enhance antibody production to target molecules by a novel mechanism.  
It can be expected to be applied to the development of highly effective vaccines. 

The research group of Professor Takeshi Tsubata and graduate students Wang Long and Shinji Kunitake at Medical Research Institute, Tokyo Medical and Dental University in collaboration with Professor Kazushige Akiyoshi and Assistant Professor Shinichi Sawada at the Graduate School of Engineering, Kyoto University developed a technology that significantly enhances antibody production to target molecules using a polysaccharide-based carrier. This research was carried out with the support of the Ministry of Education, Culture, Sports, Science and Technology's Grant-in- Aid for Scientific Research, the Mitsubishi Foundation, and the Joint Research Projects at Medical Research Institute, Tokyo Medical and Dental University. It was published in the journal “Vaccine” in the online version on November 29th, 2021.

Background of research

In order for naive T lymphocytes (T cells) that have never been activated by an antigen to be activated and elicit an immune response, T cells must be presented with antigen by antigen-presenting cells such as dendritic cells for several days. For this reason, it has been known that antigens that are not easily degraded activate T cells more strongly. However, technologies that enhance the immune response by delaying the degradation of antigens have not been developed.

Summary of research results

 In this study, a protein antigen was chemically bound to a nano-sized gel (nanogel) formed by introducing cholesteryl group to the polysaccharide pullulan to immunize mice. Almost no antibody production was observed by immunization with the protein antigen alone, but the protein antigen bound to cholesteryl pullulan induced production of a large amount of specific antibody without using an adjuvant. Dendritic cells*1 in regional lymph nodes take up the immunized antigen, and present the antigen*2 to T cells. The protein antigen was rapidly degraded in dendritic cells, but the protein antigen bound to cholesteryl pullulan was delayed in degradation. This suggests that conjugating the antigen to cholesteryl pullulan delays the degradation of the antigen in dendritic cells, resulting in significant enhancement of T cell activation and antibody production. 

Significance of research results

We have succeeded in developing a technology that enhances the immune response, including antibody production, by delaying the degradation of antigens. Using this technology, it will be possible to develop more effective vaccines.


*1 Dendritic cells: One of the immune cells, which are present in various parts of the body, especially in lymphoid tissues such as lymph nodes, skin, and mucosa. These cells take up antigens such as pathogens and present them to T cells. 
*2 Antigen presentation: Immune cells such as dendritic cells take up antigen, degrade it, and present its fragments on the cell surface. T cells are not stimulated by the antigen itself, but are stimulated and activated by the antigen presented by dendritic cells. 

Article information

“Protein antigen conjugated with cholesteryl amino-pullulan nanogel shows delayed degradation in dendritic cells and augmented immunogenicity” by Long, W., Kunitake, S., Sawada, S., Akiyoshi, K. and Tsubata, T. 
 It was published in Vaccine, Volume 39 (2021) published by Elsevier.

Copies of this paper are available to credentialed journalists upon request; please contact Elsevier's Newsroom at  or +31 20 485 2719
About Vaccine: Vaccine is the pre-eminent journal for those interested in vaccines and vaccination. It is the official journal of The Edward Jenner Society  and The Japanese Society for Vaccinology and is published by Elsevier

Correspondence to

Takeshi Tsubata,  Professor

Department of Immunology,

Medical Research Institute, 
Tokyo Medical and Dental University(TMDU)

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