I’ve been keeping up to date with the latest coronavirus vaccine developments using Derek Lowe’s blog, a resource which I cannot recommend highly enough. A recent post mentioned that vaccines developers are looking out for signs of antibody-dependent enhancement (ADE), which I vaguely remembered from my undergraduate biochemistry days researching an essay on dengue fever. ADE is an interesting immunology phenomenon, and so I thought I’d treat you all to a brief introduction to the issue.
When we are exposed to a virus, or a vaccine, we produce an immune response. This immune response includes the production of antibodies which are specific to the virus. This means if the person is later exposed to the same virus, antibodies already exist in the body which can swiftly bind and neutralise the virus. These neutralising antibodies prevent the virus attaching to host cells and cause aggregation of the virus particles, so that the virus cannot enter cells and replicate. Instead, it is destroyed by the immune system before it can infect cells.
ADE is the unfortunate process where instead of the antibodies neutralising the virus, they help the virus get into cells. The mechanisms for this are not yet fully understood and it’s likely that there are multiple different ways it occurs, depending on the virus and cell types. The most well-known occurrence is in dengue fever, and these sabotaging antibodies have also been reported in influenza, HIV and coronaviruses. When infected with the dengue virus, some people show no, or very mild, symptoms, whereas as others develop series clinical complications. Part of the reason underlying this vast difference in response is the different strains of dengue virus, known as serotypes. If a person has previously been infected with one serotype and later is infected with another serotype, they sometimes have a much higher risk of getting seriously ill than they did with the first infection. This is thought to be due to some patients still having antibodies present from the first infection which can recognise and bind the new serotype, as it looks similar to the first virus, but the antibodies cannot successfully neutralise the virus. Instead, having bound the virus, the antibody also binds to Fc receptors on cell surfaces, triggering a process called endocytosis – causing the virus and antibody to enter the cell.
With coronaviruses, there have been reports linking antibodies which bind to the SARS-CoV spike protein to symptoms of ADE, including causing lung injury [1]. In February, a novel mechanism was proposed where antibodies cause a conformational change in the spike protein when they bind to it, making virus entry into cells easier [2].
Fortunately, no signs of ADE have been reported in the current coronavirus vaccine front-runners, and this is not a call for us all to panic. Rather, we should marvel at the intricacies and immense complexity of the immune system.
[1] Liu, Li, et al. “Anti–spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection.” JCI insight 4.4 (2019).
[2] Wan, Yushun, et al. “Molecular mechanism for antibody-dependent enhancement of coronavirus entry.” Journal of virology 94.5 (2020).
