An experimental vaccine for respiratory syncytial virus (RSV) showed positive results in a Phase I clinical trial. Researchers from The University of Texas at Austin and others reported that a single dose of the vaccine produced significant evidence of RSV-neutralizing antibodies that were sustained for several months.
An experimental vaccine for respiratory syncytial virus (RSV) showed positive results in a Phase I clinical trial. Researchers from The University of Texas at Austin and others reported that a single dose of the vaccine produced significant evidence of RSV-neutralizing antibodies that were sustained for several months.
RSV causes lung and respiratory tract infections. It affects both children and adults and is considered so common that almost all children have been infected by the age of two. In adults and older, healthy children, RSV symptoms are mild and similar to that of the common cold. But in premature babies, older adults, infants and adults with heart and lung disease or anyone who is immunocompromised, RSV can cause severe infections. The most severe infections are typically in infants and can be life-threatening.
For children under the age of one, RSV is second to malaria for infectious disease deaths.
The development of the vaccine, DS-Cav1, was headed by Barney Graham and Peter Kwong of the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center (VRC) and U of T’s Jason McLellan, a former postdoctoral researcher at VRC.
To date, no RSV vaccine has been successfully developed. McLellan and his team used a different approach, using something called structure-based vaccine design.
The F protein is the part of RSV that causes the immune system to produce antibodies. But the F protein changes shape before and after infection. If the immune system meets the RSV virus F protein in the first shape, it creates potent antibodies. But if it encounters the protein in the second shape, not as many antibodies are created and they’re not as effective. Traditional vaccine development usually led to second-shape F proteins and ineffective antibody response.
The team used X-ray crystallography to identify the atomic-level structure of the F protein in its first shape. They then re-engineered the F protein so it couldn’t change shape—it was now fixed in the position that results in the most effective antibodies.
“Our first time testing these stabilized molecules in animals, the response was 10-fold higher than anything anyone had ever seen before,” McLellan stated. “And at that point, we’re thinking, ‘This is it. We’ve got it.’ That was exciting.”
The study was published in the journal Science and describes interim analysis of data from the first 40 adult volunteers in the trial. The data suggests the vaccine produces more than 10-fold increase in RSV-neutralizing antibodies compared to the number a person produces naturally from RSV exposure earlier in life.
The researchers are careful to note this is an early Phase I trial, which is primarily focused on safety and dosing. “It still needs to go through Phase II and Phase III, looking at efficacy such as, is it reducing the severity of disease, or is it reducing hospitalizations?” stated McLellan.
If the vaccine lives up to its potential, it could potentially be given to pregnant women in their third trimester, which would offer protection to the developing child and protect them for the first six to seven months of life, which is when most RSV infections occur.
“You give it to the mother to help protect the infant,” McLellan told KXAN TV. “We are trying to push back the age of that first infection to the point where their bodies are more robust to handle it.”
If all goes well, the vaccine could be available by 2024.
