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However, immune tolerance induced by allogeneic antigens is constrained by insufficient antigen specificity, safety risks, and transient therapeutic efficacy. Herein, we present an injectable hydrogel capable of environment-responsive, long-acting delivery of inverse vaccine nanomimics (IVNMs) to overcome these challenges. These IVNMs efficiently capture antigens released by dying cardiomyocytes through the orthogonal reaction between surface maleimide groups and antigen thiols and promote mannose-facilitated uptake by CD206-expressing immune cells, including dendritic cells (DCs). The antigens captured by IVNMs, together with the sustained release of rapamycin from IVNMs, promote the differentiation of DCs into tolerogenic DCs, leading to a persistent increase in regulatory T cells and the establishment of immune tolerance memory. In post-MI rat models, myocardial inflammation was markedly and persistently alleviated, accompanied by enhanced neovascularization and reduced fibrosis, contributing to a sustained cardioprotective effect.<\/jats:p>","DOI":"10.34133\/research.1464","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:19:16Z","timestamp":1791379156000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":0,"title":["Inverse Vaccine Nanomimics: In\u00a0situ Antigen-Specific Immune Tolerance Induction for Durable Cardiac Repair Post-Myocardial Infarction"],"prefix":"10.34133","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4067-8844","authenticated-orcid":false,"given":"Tian","family":"Yue","sequence":"first","affiliation":[{"name":"Department of Cardiology, The Third People\u2019s Hospital of Chengdu\/Affiliated Hospital of Southwest Jiaotong University, \rChengdu Institute of Cardiovascular Disease, Chengdu, China."},{"name":"School of Ecology and Environment, \rXizang University, Lhasa, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Third People\u2019s Hospital of Chengdu\/Affiliated Hospital of Southwest Jiaotong University, \rChengdu Institute of Cardiovascular Disease, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Ma","sequence":"additional","affiliation":[{"name":"The Tenth Affiliated Hospital, \rSouthern Medical University (Dongguan People\u2019s Hospital), Dongguan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"He","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Third People\u2019s Hospital of Chengdu\/Affiliated Hospital of Southwest Jiaotong University, \rChengdu Institute of Cardiovascular Disease, Chengdu, China."},{"name":"The Tenth Affiliated Hospital, \rSouthern Medical University (Dongguan People\u2019s Hospital), Dongguan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"The Tenth Affiliated Hospital, \rSouthern Medical University (Dongguan People\u2019s Hospital), Dongguan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9901-0927","authenticated-orcid":true,"given":"Zhilu","family":"Yang","sequence":"additional","affiliation":[{"name":"The Tenth Affiliated Hospital, \rSouthern Medical University (Dongguan People\u2019s Hospital), Dongguan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Third People\u2019s Hospital of Chengdu\/Affiliated Hospital of Southwest Jiaotong University, \rChengdu Institute of Cardiovascular Disease, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"issue":"9","key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1038\/s41591-023-02513-2","article-title":"A new clinical classification of acute myocardial infarction","volume":"29","author":"Lindahl B","year":"2023","unstructured":"Lindahl B, Mills NL. 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