{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T04:40:28Z","timestamp":1760676028229,"version":"build-2065373602"},"reference-count":128,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Singapore National Medical Council"},{"name":"Open-Fund Young Investigator Research Grant","award":["MOH-001259-01"],"award-info":[{"award-number":["MOH-001259-01"]}]},{"name":"TRipartite Program in Infectious Diseases Research For New Discoveries and TreatmENT","award":["TP24_P1"],"award-info":[{"award-number":["TP24_P1"]}]},{"DOI":"10.13039\/501100012415","name":"Biomedical Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012415","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001348","name":"A*STAR","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001348","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Central Research Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Antibodies are a cornerstone of the adaptive immune response, serving as key defenders against viral infections; however, they can also act as a double-edged sword, contributing to immune-mediated pathologies. This review advances a \u201cYin-Yang\u201d framework to integrate the dual activities of antibodies. The protective \u2018Yin\u2019 functions are driven by high-affinity antibodies generated through processes like somatic hypermutation and class-switch recombination. These antibodies execute viral neutralization, activate the complement system, and engage Fc receptors (FcRs) to drive antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis. These mechanisms form the immunological basis of effective vaccines, which aim to elicit durable and functionally specialized antibody isotypes like IgG and mucosal IgA. Conversely, the pathogenic \u2018Yang\u2019 of the response can be detrimental. This includes antibody-dependent enhancement (ADE) of infection, notably observed with flaviviruses, and the development of autoimmunity through mechanisms like molecular mimicry and bystander activation, which can lead to conditions such as multiple sclerosis and Guillain-Barr\u00e9 Syndrome. The balance between protection and pathology is tipped by a confluence of factors. These include viral evasion strategies like antigenic mutation and glycan shielding, as well as host-based determinants such as genetic polymorphisms in FcRs, immune history, and the gut microbiome. Understanding these molecular determinants informs the rational design of next-generation interventions. Promising strategies, such as Fc-region glyco-engineering and the design of tolerogenic vaccines, aim to selectively promote protective functions while minimizing pathological risks, offering a clear path forward in combating viral threats.<\/jats:p>","DOI":"10.3390\/diseases13100341","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T08:34:26Z","timestamp":1760517266000},"page":"341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Yin and Yang of Antibodies in Viral Infectious Diseases"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6258-5059","authenticated-orcid":false,"given":"Jianning","family":"He","sequence":"first","affiliation":[{"name":"Division of Natural and Applied Science, Duke Kunshan University, No. 8 Duke Avenue, Kunshan 215316, China"},{"name":"Rollins School of Public Health, Emory University, 1518 Clifton Road NE, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8360-9537","authenticated-orcid":false,"given":"Yiu-Wing","family":"Kam","sequence":"additional","affiliation":[{"name":"Division of Natural and Applied Science, Duke Kunshan University, No. 8 Duke Avenue, Kunshan 215316, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5645-7048","authenticated-orcid":false,"given":"Fok-Moon","family":"Lum","sequence":"additional","affiliation":[{"name":"A*STAR Infectious Diseases Labs (A*IDL), Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore"},{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1016\/j.jaci.2009.09.017","article-title":"Adaptive immunity","volume":"125","author":"Bonilla","year":"2010","journal-title":"J. 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