Antibody dependent enhancement

Antibody Dependent Enhacement (ADE) occurs when antiviral antibodies enhance viral entry into host cells, leading to increased infectivity. The most common example of ADE in during dengue infection. There are four serotypes of dengue virus, serotype 1, 2, 3 and 4. ADE occurs when a patient down with previous dengue infection is infected with dengue again but with a different serotype. These patients have severe clinical outcome and high viremia compared to patients who are down with dengue infection but have not suffered dengue infection from different serotype previously.

There are a few possibilities to explain the phenomena, using dengue as an example:

1. Viral surface protein laced with antibodies against dengue of other serotype (e.g. serotype 1) binds to dengue virus serotype 2. The binding is meant to neutralize the virus surface protein from attaching to the cell, but instead the antibody bound to virus also binds to the receptor of the cell, Fc-region antibody receptor. This brings virus to close proximity to virus-specific receptor, and the cell endocytose the virus through normal infection route.

2. Dengue virus surface protein may be attached with antibodies of different serotype and classical pathway of the complementation system may be activated. The complement cascade system is instead used to bind C1q attached to virus surface protein via antibodies, which in turn binds C1q receptor found on cells, bringing the virus and the cell close enough for specific virus receptor to bind the virus and infection begin. ¹

3. When antibody of dengue virus is present for a different serotype, the supposedly neutralizing antibodies is unable to neutralize the virus, but is nevetheless ingested into the cell as a sub-neutralized virus particle. These viruses are phagocytosed as antigen-antibody complexes targeted for degradation by macrophages. Upon ingestion the antibodies no longer even sub-neutralize the body due to denaturing condition at the step for acidification of phagosome before fusion with lysosome. The virus become active and begin its proliferation within the cell.