Systems Pharmacology-based strategy to screen new adjuvant for hepatitis B vaccine from Traditional Chinese Medicine Ophiocordyceps sinensis Jingbo Wang+, Rui Liu, Baoxiu Liu, Yan Yang, Jun Xie*, Naishuo Zhu* I Laboratory of Molecular Immunology State Key Laboratory of Genetic Engineering Institute of Biomedical Science, School of Life Sciences, Fudan University, Shanghai, 200438. China *Correspondence and requests for materials should be addresses to NZ.(Email chu@fudan.edu.cn)andJX.(Email:xiejun@fudan.edu.cn) t These authors contributed equally to this work Adjuvants are common component for many vaccines but there are still few licensed for human use due to low efficiency or side effects. The present work adopted Systems Pharmacology analysis as a new strategy to screen adjuvants from traditional Chinese medicine Ophiocordyceps sinensis has been used for many years in China and other Asian countries with many biological properties, but the pharmacological mechanism has not been fully elucidated. First in this study, 190 putative targets for 17 active compounds in Ophiocordyceps sinensis were retrieved and a systems pharmacology-based approach was applied to provide new insights into the pharmacological actions of the drug. Pathway enrichment analysis found that the targets participated in several immunological processes. Based on this, we selected cordycepin as a target compound to serve as an adjuvant of the hepatitis B vaccine because the existing vaccine often fails to induce an effective immune response in1 Systems Pharmacology-based strategy to screen new adjuvant for hepatitis B vaccine from Traditional Chinese Medicine Ophiocordyceps sinensis Jingbo Wang1+, Rui Liu1+, Baoxiu Liu1 , Yan Yang1 , Jun Xie1 *, Naishuo Zhu1 * 1 Laboratory of Molecular Immunology, State Key Laboratory of Genetic Engineering, Institute of Biomedical Science, School of Life Sciences, Fudan University, Shanghai, 200438, China. *Correspondence and requests for materials should be addresses to N.Z. (Email: nzhu@fudan.edu.cn) and J.X. (Email:xiejun@fudan.edu.cn) + These authors contributed equally to this work. Adjuvants are common component for many vaccines but there are still few licensed for human use due to low efficiency or side effects. The present work adopted Systems Pharmacology analysis as a new strategy to screen adjuvants from traditional Chinese medicine. Ophiocordyceps sinensis has been used for many years in China and other Asian countries with many biological properties, but the pharmacological mechanism has not been fully elucidated. First in this study, 190 putative targets for 17 active compounds in Ophiocordyceps sinensis were retrieved and a systems pharmacology-based approach was applied to provide new insights into the pharmacological actions of the drug. Pathway enrichment analysis found that the targets participated in several immunological processes. Based on this, we selected cordycepin as a target compound to serve as an adjuvant of the hepatitis B vaccine because the existing vaccine often fails to induce an effective immune response in