Antibody-Dependent Enhancement in Dengue

Antibody-dependent enhancement (ADE) occurs when antibodies bind a virus but do not neutralize it effectively, and instead facilitate its entry into susceptible immune cells. In dengue, antibodies from an earlier infection with one serotype may enhance infection during a later exposure to a different serotype, increasing the risk of severe dengue.

Mechanism during secondary infection

Dengue virus has four antigenically distinct serotypes. Infection generally produces durable protection against the infecting serotype, but cross-reactive protection against other serotypes may be incomplete or temporary.

• During a later heterologous infection, pre-existing antibodies may bind the new serotype without blocking its infectivity.
• The antibody-virus complexes attach to Fc gamma receptors on monocytes, macrophages and related cells, facilitating viral entry and replication.
• This mechanism can produce higher viraemia than would occur with an effective neutralizing antibody response.

How enhancement increases severity

Greater infection of susceptible immune cells can amplify viral replication and dysregulated inflammatory responses. The resulting endothelial dysfunction and increased vascular permeability contribute to plasma leakage, a defining feature of severe dengue.

• Plasma leakage can cause haemoconcentration, fluid accumulation and circulatory shock.
• Severe disease may also involve bleeding, thrombocytopenia or serious organ impairment.
• ADE increases risk but does not make severe disease inevitable; antibody concentration, infecting serotype and host immune factors also influence the outcome.

Significance for dengue vaccination

A dengue vaccine should induce sufficiently strong and balanced neutralizing immunity against all four serotypes. An uneven or inadequate antibody response is a concern because antibodies that bind without effective neutralization could theoretically create conditions resembling a secondary heterologous infection.

• Vaccine evaluation must therefore assess serotype-specific protection, prior dengue exposure and the duration of immunity.
• Vaccination complements, rather than replaces, vector control and prevention of mosquito bites.

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