An adjuvant database for preclinical evaluation of vaccines and immunotherapeutics

Yayoi Natsume-Kitatani; Kouji Kobiyama; Yoshinobu Igarashi; Taiki Aoshi; Noriyuki Nakatsu; Lokesh P Tripathi; Junichi Ito; Johan Nyström-Persson; Yuji Kosugi; Rodolfo S Allendes Osorio; Chioko Nagao; Burcu Temizoz; Etsushi Kuroda; Daron M Standley; Hiroshi Kiyono; Kenji Nakanishi; Satoshi Uematsu; Isao Hamaguchi; Yasuhiro Yasutomi; Jun Kunisawa; Sho Yamasaki; Cevayir Coban; Hiroshi Yamada; Kenji Mizuguchi; Ken J Ishii

doi:10.1016/j.chembiol.2025.07.005

An adjuvant database for preclinical evaluation of vaccines and immunotherapeutics

Cell Chem Biol. 2025 Aug 21;32(8):1075-1088.e3. doi: 10.1016/j.chembiol.2025.07.005. Epub 2025 Aug 11.

Authors

Yayoi Natsume-Kitatani¹, Kouji Kobiyama², Yoshinobu Igarashi³, Taiki Aoshi⁴, Noriyuki Nakatsu³, Lokesh P Tripathi⁵, Junichi Ito⁶, Johan Nyström-Persson⁷, Yuji Kosugi⁸, Rodolfo S Allendes Osorio⁹, Chioko Nagao¹⁰, Burcu Temizoz¹¹, Etsushi Kuroda¹², Daron M Standley¹³, Hiroshi Kiyono¹⁴, Kenji Nakanishi¹², Satoshi Uematsu¹⁵, Isao Hamaguchi¹⁶, Yasuhiro Yasutomi¹⁷, Jun Kunisawa¹⁸, Sho Yamasaki¹⁹, Cevayir Coban²⁰, Hiroshi Yamada³, Kenji Mizuguchi¹⁰, Ken J Ishii²¹

Affiliations

¹ Laboratory of Bioinformatics, Artificial Intelligence Center for Health and Biomedical Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBN), Settsu, Osaka 566-0002, Japan; Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Tokushima 770-8503, Japan; Institute for Protein Research, the University of Osaka, Suita, Osaka 565-0871, Japan.
² Laboratory of Vaccine Science, the Institute of Medical Science, the University of Tokyo (IMSUT), Minato-ku, Tokyo 108-8639, Japan; International Vaccine Design Center (VDesC), the Institute of Medical Science, the University of Tokyo (IMSUT), Minato-ku, Tokyo 108-8639, Japan; Division of Rheumatology, Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0809, USA.
³ Toxicogenomics-Informatics Project, Artificial Intelligence Center for Health and Biomedical Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBN), Settsu, Osaka 567-0085, Japan.
⁴ Department of Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan.
⁵ Laboratory of Bioinformatics, Artificial Intelligence Center for Health and Biomedical Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBN), Settsu, Osaka 566-0002, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
⁶ Discovery Concept Validation Function, Eisai Co., Ltd., Kobe, Hyogo 650-0047, Japan.
⁷ JNP Solutions, Sumida-ku, Tokyo 130-0015, Japan.
⁸ Lifematics Ltd., Chuo-ku, Tokyo 104-0032, Japan.
⁹ Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), the University of Osaka, Suita, Osaka 565-0871, Japan.
¹⁰ Institute for Protein Research, the University of Osaka, Suita, Osaka 565-0871, Japan.
¹¹ Laboratory of Vaccine Science, the Institute of Medical Science, the University of Tokyo (IMSUT), Minato-ku, Tokyo 108-8639, Japan.
¹² Department of Immunology, Hyogo Medical University School of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
¹³ Department of Genome Informatics, Genome Information Research Center, Research Institute for Microbial Diseases (RIMD), the University of Osaka, Suita, Osaka 565-0871, Japan.
¹⁴ Department of Human Mucosal Vaccinology, Chiba University Hospital, Chiba 260-8670, Japan; Synergy Institute for Futuristic Mucosal Vaccine Research and Development (cSIMVa), Chiba University, Chiba, Chiba 260-8670, Japan; CU-UCSD Center for Mucosal Immunology, Allergy and Vaccines (cMAV), UC San Diego School of Medicine, San Diego, CA 92093-0063, USA.
¹⁵ Department of Immunology and Genomics, Graduate School of Medicine, Osaka Metropolitan University, Abeno, Osaka 545-0051, Japan; Division of Metagenome Medicine, Human Genome Center, the Institute of Medical Science, the University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
¹⁶ Research Center for Biological Products in the Next Generation, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan.
¹⁷ Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition (NIBN), Tsukuba, Ibaraki 305-0843, Japan.
¹⁸ Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBN), Ibaraki, Osaka 567-0085, Japan.
¹⁹ Department of Molecular Immunology, Research Institute for Microbial Diseases (RIMD), the University of Osaka, Suita, Osaka 565-0871, Japan; Laboratory of Molecular Immunology, Immunology Frontier Research Center (IFReC), the University of Osaka, Suita, Osaka 565-0871, Japan; Center for Infectious Disease Education and Research (CiDER), the University of Osaka, Suita, Osaka 565-0871, Japan; Center for Advanced Modalities and DDS (CAMaD), the University of Osaka, Suita, Osaka 565-0871, Japan.
²⁰ International Vaccine Design Center (VDesC), the Institute of Medical Science, the University of Tokyo (IMSUT), Minato-ku, Tokyo 108-8639, Japan; Division of Malaria Immunology, Department of Microbiology and Immunology, The Institute of Medical Science (IMSUT), the University of Tokyo, Tokyo 108-8639, Japan; WPI Immunology Frontier Research Center (IFReC), the University of Osaka, Suita, Osaka 565-0871, Japan; The University of Tokyo Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), the University of Tokyo, Tokyo 108-8639, Japan.
²¹ Laboratory of Vaccine Science, the Institute of Medical Science, the University of Tokyo (IMSUT), Minato-ku, Tokyo 108-8639, Japan; International Vaccine Design Center (VDesC), the Institute of Medical Science, the University of Tokyo (IMSUT), Minato-ku, Tokyo 108-8639, Japan; WPI Immunology Frontier Research Center (IFReC), the University of Osaka, Suita, Osaka 565-0871, Japan; The University of Tokyo Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), the University of Tokyo, Tokyo 108-8639, Japan. Electronic address: kenishii@ims.u-tokyo.ac.jp.

PMID: 40795871
DOI: 10.1016/j.chembiol.2025.07.005

Abstract

Adjuvants are immunostimulators used to enhance vaccine efficacy against infectious diseases. However, current methods for evaluating their efficacy and safety are limited, hindering large-scale screening. To address this, we developed a prototype Adjuvant Database (ADB) containing transcriptome data, generated using the same protocols as the widely used Open TG-GATEs (OTG) toxicogenomics database, covering 25 adjuvants across multiple species, organs, time points, and doses. This enabled cross-database integration of ADB and OTG. Transcriptomic patterns successfully distinguished each adjuvant regardless of organs or species. Using both databases, we built machine learning models to predict adjuvanticity and hepatotoxicity. Notably, we identified colchicine's adjuvant activity and FK565's liver toxicity through data-driven analysis. Overall, ADB combined with OTG offers a framework for transcriptomics-based, data-driven screening of adjuvant candidates.

Keywords: NOD1; RLR; STING; TLR; adjuvant; innate immunity; machine learning; pharmacology; toxicology; vaccine.

MeSH terms

Adjuvants, Immunologic* / chemistry
Adjuvants, Immunologic* / pharmacology
Animals
Databases, Factual*
Drug Evaluation, Preclinical
Humans
Immunotherapy*
Machine Learning
Mice
Transcriptome / drug effects
Vaccines*

Substances

Adjuvants, Immunologic
Vaccines