REVIEW: Molecular Mechanisms of Antibody-Dependent Enhancement of Viral Infection

---

Alexander V. Filatov^1,2,a*, Maria G. Byazrova^1,3, Maria M. Sukhova^1,2, and Alexey G. Prilipov^1,4

¹National Research Center Institute of Immunology, Federal Medical Biological Agency of Russia, 115522 Moscow, Russia

²Department of Immunology, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia

³Peoples’ Friendship University, Ministry of Science and Higher Education of the Russian Federation, 117198 Moscow, Russia

⁴Gamaleya Federal Research Centre of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia

^* To whom correspondence should be addressed.

Received: August 29, 2025; Revised: September 26, 2025; Accepted: October 24, 2025

---

Antibody-dependent enhancement (ADE) of infection is a phenomenon observed during secondary infection caused by some viruses (primarily, from the Flaviviridae family), including dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), tick-borne encephalitis virus, yellow fever virus, and some others. There are two types of ADE mediated by (i) Fc receptors and (ii) receptors for complement system components. The first type involves 4 types of Fc receptors for IgG molecules (FcRI, FcRIIa, FcRIIb, and FcRIIIa) which ensure the binding of the virus-antibody complex to the target cell and its subsequent internalization. The Fc-mediated uptake of the virus is an active process that involves a number of signaling molecules and triggers branched cascades of activation events. The Fc-mediated pathway of viral entry increases the viral load and switches the cell from the antiviral response to the proinflammatory pathway, thus promoting more efficient viral replication. Unlike other Fc receptors, FcRIIb bound to IgG inhibits the capture of the virus–antibody complex and prevents the ADE. The development of ADE in response to vaccination is highly undesirable. Understanding the biochemical mechanisms underlying ADE is important for the development of new vaccines and therapeutic monoclonal antibodies for protecting against viral infections.

---

KEY WORDS: antibody-dependent enhancement of infection, Fc receptors, ITAM and ITIM motifs, dengue virus, Ebola virus, West Nile virus, Zika virus, vaccine-associated enhancement of infection

DOI: 10.1134/S0006297925602795

Publisher’s Note. Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

---