The Zika outbreak of 2015 and 2016 left lasting consequences for children who were in the womb when their mothers were infected with the virus, and now researchers are investigating a safe vaccine that will not negatively interact with certain other viruses.
Zika is a flavivirus, a family which includes dengue, West Nile, and yellow fever virus. In order to protect against these and other pathogens, “we have the ability to make a huge diversity of antibodies, and if we get infected or vaccinated, those antibodies recognise the pathogen,” explained first author Shannon Esswein, a graduate student at the California Institute of Technology.
However, when getting sick with a virus a second time, the body’s own immune response can worsen the situation. Known as antibody-dependent enhancement (ADE), this is when the antibodies stick to the outside of the virus but not neutralising its ability to lock onto cells. This can inadvertently help the virus to infect more cells by letting it enter cells the antibodies are sticking to. A recent study sought to investigate whether this could happen with monoclonal antibody treatments for COVID.
In order to prevent ADE when creating a vaccine, knowing how antibodies adhere to a specific virus is crucial for scientists. In the case flaviviruses, this is especially important as antibodies that protect against one flavivirus may also stick to, but not protect against other flaviviruses, raising the risk of ADE. Antibodies generated in response to a Zika virus vaccine could trigger ADE, if that person is exposed to other flaviviruses such as dengue.
To understand this, the researchers looked at a portion of the flavivirus called the envelope domain III protein, which has been shown to be an important target for protective antibodies fighting flavivirus infections. They studied how those antibodies changed over time as they matured and became better able to adhere to the Zika virus. They also looked at how the antibodies cross-reacted with other flaviviruses, including the four dengue virus types. Their results showed that the Zika antibodies also tightly stick to and defend against dengue type 1, but only weakly stick to West Nile and dengue types 2 and 4. “The weak cross-reactivity of these antibodies doesn’t seem to defend against those flaviviruses, but also doesn’t induce ADE,” Esswein said. These results suggest that the envelope domain III could be a useful basis for a safe vaccine. They also described structures demonstrating how two antibodies recognise Zika and West Nile envelope domain III.
The study results demonstrate how the body mounts “a potent immune response to Zika virus,” said Esswein. Insights gained on the antibodies involved in this immune response will aid the development of new vaccines.
Source: Medical Xpress
Journal information: Shannon R. Esswein et al. Structural basis for Zika envelope domain III recognition by a germline version of a recurrent neutralizing antibody, Proceedings of the National Academy of Sciences (2020). DOI: 10.1073/pnas.1919269117
