Respiratory syncytial virus (RSV) is a common and potentially dangerous virus for which no vaccine currently exists despite decades of effort from the scientific community. Associate Professor of Biomolecular Engineering at the Baskin School of Engineering Rebecca DuBois has set out to address this pressing need. To fund her innovative approach to the development of an RSV vaccine, DuBois has been awarded the prestigious and highly competitive National Institutes of Health Research Project Grant (RO1).
RSV causes contagious cold-like symptoms that can develop into serious lung problems and lead to hospitalizations, especially in young children and older populations – each year, 3 million children under five years old are hospitalized from RSV and 64 million total people are affected worldwide.The five-year, $3.8 million grant will be shared with DuBois’s collaborator Ralph Tripp at the University of Georgia and will build on both researchers' years of work studying RSV. Their overall aim is to validate their RSV vaccine in pre-clinical trials.
“There’s a huge need – this is a really important gap in our vaccine schedule to protect children,” said DuBois, whose experience with her child’s severe RSV fueled her to take on this research. “I think the NIH study section reviewers liked that it's a totally different strategy than what everyone else is taking.”
DuBois’s lab focuses on bioengineering the commonly overlooked RSV G protein, used by the virus to attach to host cells, to expose its vulnerable points so the host’s body can fight back.
In previous work, they have found that a region, called the central conserved domain and just 40 amino acids long, can be engineered to evoke an protective immunogenic response from the host. Additionally, a recent paper from the DuBois lab determined that this altered protein is still recognized by the body’s immune system and therefore could be effective in a vaccine.
“I think since RSV has been such a difficult virus to create a vaccine for, we're innovative in that we are using structural biology to learn more about this protein and make changes to it using protein engineering to improve its immunogenicity,” said Maria Juarez, a third-year Ph.D. student in the DuBois lab. “That’s something that our lab has really spearheaded.”
Targeting this specific region of the G protein, which remains unchanged as the virus mutates, is a cutting-edge technique in vaccine development that may allow a vaccine to continue its effectiveness as the virus mutates.
“By whittling down our vaccine to this important and conserved part, and designing it so [the antigen] is exposed to our immune system in a better way, we can refocus the antibody response – it won’t get distracted by all the parts that aren’t conserved,” DuBois said. “It’s a more strategic way to do vaccine design, instead of just targeting the whole protein and choosing one strain to target.”
Juarez and the others in the DuBois lab will continue to experiment with ways to ensure that the surface of their engineered protein is structured in a way to provoke the strongest immune response. Juarez also noted that the techniques she is using to engineer the protein are cheaper and less time intensive than other methods, making future production of the vaccine scalable so it can eventually be used commercially around the world.
Once DuBois’s group has developed their vaccine, they will send it to Tripp’s lab to test if it creates a strong antibody response in pre-clinical models. The group expects the first vaccines to be tested in pre-clinical models by the end of 2022.
This project differs from other RSV vaccine efforts, some of which are in phase III clinical trials, in the method it uses to evoke a protective immune response. The large majority of other researchers focus on the RSV F protein, which fuses the virus and host cell membranes together to get the virus’s genetic information into cells.
Eventually, the researchers anticipate that their vaccine could be combined with one that uses the F protein in order to create an even more robust immune response.
