A Review: Understanding Molecular Mechanisms of Antibody-Dependent Enhancement in Viral Infections

Abstract

Antibody Dependent Enhancement (ADE) of an infection has been of interest in the investigation of many viruses. It is associated with the severity of the infection. ADE is mediated by non-neutralizing antibodies, antibodies at sub-neutralizing concentrations, or cross-reactive non-neutralizing antibodies. Treatments like plasma therapy, B cell immunizations, and antibody therapies may trigger ADE. It is seen as an impediment to vaccine development as well. In viruses including the Dengue virus (DENV), severe acute respiratory syndrome (SARS) virus, Middle East respiratory syndrome (MERS) virus, human immunodeficiency virus (HIV), Ebola virus, Zika virus, and influenza virus, the likely mechanisms of ADE are postulated and described. ADE improves the likelihood of productively infecting cells that are expressing the complement receptor or the Fc receptor (FcR) rather than the viral receptors. ADE occurs when the FcR, particularly the Fc gamma receptor, and/or complement system, particularly Complement 1q (C1q), allow the entry of the virus-antibody complex into the cell. Moreover, ADE alters the innate immune pathways to escape from lysis, promoting viral replication inside the cell that produces viral particles. This review discusses the involvement of FcR and the downstream immunomodulatory pathways in ADE, the complement system, and innate antiviral signaling pathways modification in ADE and its impact on facilitating viral replication. Additionally, we have outlined the modes of ADE in the cases of different viruses reported until now.

Beyond bNAbs: Uses, Risks, and Opportunities for Therapeutic Application of Non-Neutralising Antibodies in Viral Infection

“…Extrinsic ADE is observed when antibodies elicited by primary infection increase the risk of severe disease upon secondary infection with the same or a closely related virus [ 83 , 84 ] ( Figure 2 ). In contrast, intrinsic ADE facilitates enhanced viral replication through suppression of host antiviral responses [ 85 , 86 ] ( Figure 2 ). ADE is of great importance in Dengue virus (DENV) infection, with secondary infection the greatest risk factor for dengue haemorrhagic fever/dengue shock syndrome [ 87 ].…”

Beyond bnAbs: Uses, Risks, and Opportunities for Therapeutic Application of Non-neutralising Antibodies in Viral Infection

“…Extrinsic ADE is observed when antibodies elicited by primary infection increase risk of severe disease upon secondary infection with the same or a closely related virus [83,84] (Figure 2). In contrast, intrinsic ADE facilitates enhanced viral replication through suppression of host antiviral responses [85,86] (Figure 2). ADE is of great importance in Dengue virus (DENV) infection, with secondary infection the greatest risk factor for dengue haemorrhagic fever/dengue shock syndrome [87].…”

Unveiling a Shield of Hope: A Novel Multiepitope-Based Immunogen for Cross-Serotype Cellular Defense against Dengue Virus

“…values; sign change is only for consistency, where higher values are associated with higher predicted efficiency. 4 Processing score combines the proteasome and TAP scores. It predicts a quantity proportional to the amount of peptide present in the ER, where a peptide can bind to multiple MHC molecules.…”

“…Instead, these antibodies may inadvertently enhance viral entry and promote viral replication within immune cells, a phenomenon known as antibody-dependent enhancement (ADE). ADE may lead to an exaggerated immune response and an overproduction of inflammatory cytokines, contributing to the severity of the disease [ 4 ]. Over half of the world’s population is at risk of DENV infection and its prevalence is expected to grow, driven by the forces of climate change and urbanization [ 5 , 6 ].…”