{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T06:15:10Z","timestamp":1783318510703,"version":"3.54.6"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Antibody-dependent enhancement (ADE) is a paradoxical immunological phenomenon in which pre-existing antibodies facilitate viral entry into host cells rather than conferring protection. ADE has been extensively characterised in flaviviral systems, most notably dengue virus (DENV), and presents a significant challenge for vaccine development and antibody-based therapeutic design. In coronavirus infections, ADE may operate through both classical Fc gamma receptor (Fc\u03b3R)-mediated pathways and an intrinsic signalling mechanism involving inhibitory Fc\u03b3RIIb-mediated suppression of the type I interferon (IFN-I) response. Of critical translational relevance is the functionally demonstrated cooperative Fc\u03b3R\u2013ACE2 entry model for SARS-CoV-2, wherein virus\u2013antibody immune complexes engage Fc\u03b3 receptors and require ACE2 interaction for efficient enhancement. For SARS-CoV-2 specifically, ADE magnitude appears to be determined by an antibody\u2019s capacity to block spike\u2013ACE2 interaction rather than its neutralisation potency\n                    <jats:italic>in vitro<\/jats:italic>\n                    \u2014a finding distinct from FIPV and other coronavirus ADE systems where classical Fc\u03b3R-mediated mechanisms predominate without ACE2 co-receptor dependency. Feline infectious peritonitis virus (FIPV) represents one of the most rigorously documented biological systems in which antibody-mediated macrophage infection directly determines systemic disease outcome. This comprehensive review integrates current knowledge of Fc\u03b3R biology, IgG subclass dynamics, antibody glycosylation, coronavirus cell entry mechanisms, intracellular signalling cascades, cytokine dysregulation, comparative veterinary immunopathology, and nano-engineered immunomodulatory platforms for ADE-safe vaccine development. No confirmed clinical ADE has been documented to date in mRNA-vaccinated populations, though theoretical risk windows and population-specific vulnerabilities are critically discussed.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1859321","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T05:37:09Z","timestamp":1783316229000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Fc\u03b3R\u2013ACE2 cooperative antibody-dependent enhancement in human and veterinary coronaviruses: mechanistic insights, comparative immunology, and implications for nano-engineered immunomodulatory platforms"],"prefix":"10.3389","volume":"17","author":[{"given":"Harishkumar Jeethalu","family":"Neelakantan","sequence":"first","affiliation":[{"name":"Department of Veterinary Pharmacology and Toxicology, Veterinary College and Research Institute, Tamil Nadu Veterinary and Animal Sciences University 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