Researchers from the Walter Reed Army Institute of Research found that Dengue virus antibodies promote Zika virus infection, possibly contributing to cases of microcephaly.
When people become infected with one serotype of Dengue virus, their bodies make antibodies. If they later become infected with a different serotype of Dengue, those existing antibodies bind the virus and signal Fc receptors on cells like macrophages - this causes the macrophages to take up the virus/antibody particles, facilitating infection through a process called “antibody-dependent enhancement”.
Because Dengue and Zika are structurally similar viruses, researchers thought that antibody-dependent enhancement might also occur in people who became infected with Zika virus after they had been infected with Dengue. They tested this hypothesis using monoclonal antibodies to the Dengue E glycoprotein, which shares the same structure as the Zika E glycoprotein.
The researchers mixed the Dengue antibodies with Zika virus and exposed them to cells that had Fc receptors. The Dengue antibodies enhanced the Zika infection almost 100-fold! The Zika infection could be prevented by blocking the Fc receptors with anti-Fc receptor antibodies, indicating that antibody-dependent enhancement was taking place.
These findings spell trouble for Dengue vaccines like Dengvaxia and TV003, since they may actually enhance Zika infection. Not to mention, Zika infection may enhance future Dengue infections.
According to study authors, “we know little about the reciprocal response of anti-Zika antibodies and their capacity to enhance Dengue virus infections, although it would seem plausible that anti-Zika antibodies might similarly enhance Dengue virus. A clear understanding of the interplay between Zika and Dengue infections will be critical to Zika planning and response efforts in regions where Zika and Dengue co-circulate, and particularly valuable for vaccine design and implementation strategies for both Zika and Dengue.