“Antibody Dependent Enhancement (ADE): A Potential Hurdle for Coronavirus Vaccine Development: Due to the presence of different strains of coronavirus and the strong structural homology between the two RBD of SARS-CoV and SARS-CoV-2, the cross-reactivity between antibodies of different coronaviruses must be taken into consideration for SARS-CoV-2 vaccine development. Antibodies have a dual role in controlling infections in which either they neutralize the infection or enhance pathogen uptake. Several viruses rely on pre-existing antiviral antibodies for their entry into the target cells, a mechanism known as antibody-dependent enhancement (ADE). Pre-existing antiviral antibodies from heterologous strains can prevent the virus entry to the cells by blocking the binding to its natural receptor on the host cell surface. However, these antibodies could facilitate the entry of the virus to host cells through either interaction of the antibody-virus complex with FcR receptors on various immune cells or complement receptors by activating the complement classical pathway. Both mechanisms tend to be linked to disease exacerbation. Generally, ADE educes sustained inflammation, lymphopenia, and potentially, cytokine storm, causing severe illness, or death. Furthermore, ADE has been observed in a variety of viruses including flaviviruses, HIV, and Ebola virus. Importantly, ADE has been extensively studied in dengue viral infections since ADE has been linked to the severity of dengue shock syndrome. It should be noted that ADE was linked to some vaccines, as this was demonstrated in the efficacy trials of the tetravalent dengue vaccine (CYD-TDV). In the CYD-TDV trial, they found that seronegative individuals who received CYD-TDV suffered severe dengue disease that mimics the natural secondary infection unlike seropositive individuals who had been exposed to dengue before vaccination.
Recently, a study demonstrated that ADE occurs not only through the typical mechanism of the presence of sub-neutralizing antibodies but also that neutralizing antibodies against RBD [receptor binding domain] might be involved in ADE. This mechanism depends on the affinity, the amount, and the specificity of the antibodies. Furthermore, from a different group, the cross reactivity of anti-RBD polyclonal antibodies specific for SARS-CoV with RBD protein of SARS-CoV-2 pseudovirus was demonstrated. Moreover, ADE phenomena have been identified in SARS-CoV infections, and now potentially COVID-19. It could be hypothesized that ADE has a role in the high mortality rate in China.
The high mortality rate in some countries over the others could be due to prior exposure of one or more mild strains of similar coronaviruses. The data obtained from patients of Hubei region showed lymphopenia and sustained inflammation in most of the severe and death cases. Based on the previous information, individuals suffering the most severe disease of COVID-19 may experience the effects of antibody dependent enhancement (ADE). ADE as a complication of COVID19 should be at the forefront while developing SARS-COV-2 vaccines to avoid similar mistakes in other vaccine development like the dengue vaccine”
© 2020 Alturki, Alturki, Connors, Cusimano, Kutzler, Izmirly and Haddad. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.