In 2015, a team of six researchers received a $6.75 million program project grant from the National Institutes of Health to study immune responses to RSV with the ultimate goal of developing a vaccine candidate.
The team spans multiple areas of expertise and three research institutions: Nationwide Children’s Hospital, The Ohio State University and the University of South Florida. Its principal investigators include Octavio Ramilo, MD, Asuncion Mejias, MD, PhD, Mark Peeples, PhD, Jianrong Li, DVM, PhD, Stefan Niewiesk, DVM, PhD, and Michael Teng, PhD.
The team has published more than 46 peer-reviewed articles based on grant-funded research. And even more importantly, they’ve achieved their initial goal of developing a vaccine candidate for RSV.
Research by the team, including their 2020 publication in Science Translational Medicine, profiled immune responses in children with mild and severe RSV and led to an insight in clinical outcomes and a recommendation that for children with severe RSV, steroids should be avoided.
“By defining what a protective immune profile looks like, we can design the vaccine candidates that should stimulate that response,” says Dr. Mejias. “For example, we know based on in vivo and in vitro studies that higher levels of IL-6 indicate a more severe illness. But higher levels of IP-10 are protective. Understanding a ‘good’ immune response is critical to our success in developing an effective vaccine.”
The team’s novel vaccine candidate, described in the Journal of Virology, uses recombinant RSV carrying mutations in two viral proteins, one in the RSV G protein that attaches the virus to the ciliated cells lining the airways, and one in the RSV polymerase protein that replicates the virus genome.
“We learned several years ago that the G protein is cut when RSV is produced in cultured cells, making the virus less able to infect the cells lining the nose. We located the site of the cut and mutated it to prevent this cleavage. As a result, we increased the amount of vaccine produced by 5 times,” says Dr. Peeples.
The vaccine candidate was evaluated in the cotton rat model for in vivo immunogenicity and protection. Intranasal delivery of a small dose of the RSV vaccine candidate provided complete protection of both the upper and lower respiratory tracts.