A huge development in bioengineered RSV protein vaccine

Close encounters with infectious disease, a research team explain that Respiratory syncytial virus (RSV), causes common and sometimes dangerous respiratory disease for which there is currently no vaccine. With the publication of their work "Structure-based design and antigenic validation of respiratory syncytial virus G immunogens" in the Journal of Virology, the two researchers have reached a crucial milestone in their quest to develop an effective vaccine for the virus.

When Nuez Castrejon, a fifth-year Baskin Engineering student and the paper's lead author, was an undergraduate student, a bout of pneumonia that lasted months inspired her interest in investigating respiratory disorders. DuBois became interested in RSV after seeing her child suffer from a terrible infection of the virus, which may cause severe respiratory infections in newborns, children, and the elderly.

"We have all of these fantastic childhood immunizations that have eliminated so much childhood sickness, but there are still a number of infectious diseases that are incredibly terrible on kids, and RSV is one of them," DuBois said.

The team is now concentrating on redesigning the structure of RSV's G protein, which is responsible for attaching the virus to host cells. The scientists changed the protein's structure to avoid the detrimental effects while still triggering a protective immune response in the form of antibodies that bind to the G protein.

In a publication published in 2021, the researchers demonstrated that their modified G protein may elicit a greater antibody response than the normal G protein. However, it was unclear if the altered G protein on the virus's surface "looked like" the original protein. The latest research shows that this synthetic G protein has the same appearance as the natural G protein and is identified by human RSV-fighting antibodies.

They demonstrated that the manufactured mutation in the protein did not impair antibodies' capacity to bind it, implying that when it is employed as a vaccine antigen, these protective antibodies can be elicited in animal models, and that people will be protected from the disease in the future.

This paper is similar to a 2017 publication that was pivotal in the development of the COVID-19 vaccine and described how to bioengineer the coronavirus's Spike antigen to induce more and better antibodies, a strategy that was used to develop the Moderna, Pfizer, J&J, and Novavax vaccine Spike antigens. Both publications use structural biology to ensure that a manufactured virus is identified by the immune system and can be used to fight the real virus.

"This is the same kind of basic work that enabled scientists to design the coronavirus vaccine so rapidly and make it look exactly like the virus's surface, if not better," DuBois said. "I think what people are realising is that if we can create antigens in a way that really exposes the virus's weaknesses, we can make vaccines that activate immune responses that are better than infection."

In their approach to researching the virus's proteins, DuBois' research varies from prior efforts to build an RSV vaccine. Many researchers are working to change the shape of the RSV F protein, which fuses the virus's genetic information into cells by fusing the virus's and host cell membranes together.

However, late-stage clinical studies of vaccines based on this technique reveal only 60 to 70% protection against infection, which is promising but less than ideal for a major pathogen like RSV.

In the short term, the researchers want to examine data from partners at the University of Georgia to see how their modified protein affects illness symptoms in mice, and they'll keep working on improving the RSV G protein to elicit greater immune responses. They plan to develop an RSV vaccine that is ready for clinical trials in the next five years utilising their modified protein.

Reference:

Ana M. Nuñez Castrejon, Sara M. O’Rourke, Lawrence M. Kauvar, Rebecca M. DuBois. Structure-Based Design and Antigenic Validation of Respiratory Syncytial Virus G Immunogens. Journal of Virology, 2022; DOI: 10.1128/jvi.02201-21