Antibody-Dependent Enhancement

Antibody-dependent enhancement (ADE) is a phenomenon in which antibodies bind to a virus but do not neutralize it effectively and instead facilitate infection of certain immune cells. In dengue, antibodies generated against one serotype may be only partially effective against another serotype, allowing antibody-virus complexes to enter Fc-receptor-bearing cells and potentially increase viral replication and disease severity.

Dengue serotypes and immune response

Dengue virus has four antigenically related serotypes, designated DENV-1 to DENV-4. Infection produces strong protection against the infecting serotype, but protection against the other serotypes is limited and may be temporary.

• A later infection with the same serotype is generally neutralized by serotype-specific immunity.
• A later infection with a different serotype is called a secondary heterotypic infection.
• Pre-existing cross-reactive antibodies may recognize the new serotype without neutralizing it adequately.

How antibody-dependent enhancement occurs

During a heterotypic secondary infection, sub-neutralizing antibodies bind to the new dengue serotype. The resulting antibody-virus complexes attach through the antibody's Fc portion to Fc gamma receptors on susceptible immune cells, especially monocytes and macrophages.

• Fc-receptor-mediated uptake can increase the number of infected cells.
• Enhanced infection can produce a higher viral burden and amplify immune activation.
• ADE is therefore an unintended consequence of incomplete rather than fully neutralizing antibody protection.

Why secondary dengue can be more severe

Greater viral replication and an amplified immune response can promote inflammatory mediator release, endothelial dysfunction and increased vascular permeability. These changes may contribute to plasma leakage, shock, severe bleeding or organ impairment, the principal forms of severe dengue.

• A secondary infection with a different serotype carries a higher risk of severe dengue, but severe disease is not inevitable.
• Primary dengue infections can also become severe.
• Disease outcome also depends on viral characteristics, host factors and the overall immune response; ADE is an important mechanism, not the sole explanation.

How UPSC asks this