A team of investigators led by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), the Pirbright Institute, U.K., and the Institute for Research in Biomedicine in Switzerland has developed a novel vaccine that can protect cattle from respiratory syncytial virus (RSV) infection. The RSV strain that the researchers used for this study naturally infects cattle and is closely related to human RSV. The results suggest that a similar human RSV vaccine construct may provide protection to humans.
The findings from this study were published recently in NPJ Vaccines through an article entitled “Protection of Calves by a Prefusion-Stabilized Bovine RSV F Vaccine.”
RSV is a primary cause of respiratory disease in cattle, resulting in significant economic costs to the industry. In humans, RSV can cause serious bronchiolitis and pneumonia in young children and the elderly, as well as adults with compromised immune systems. RSV infections are estimated to cause more than 250,000 human deaths annually around the world. There is no licensed vaccine to prevent RSV infection in humans, and vaccines currently in use for cattle have noted safety and effectiveness problems.
For the current study, the research team created an investigational vaccine containing a single structurally engineered RSV protein that elicited high levels of neutralizing antibodies in mice. The protein is a stabilized version of the RSV fusion (F) glycoprotein in its initial conformation, called pre-F. Other vaccines have used the same protein in its final conformation (called post-F), but investigators found the immune response to that vaccine was much lower.
We used “a combination of structure-based design, antigenic characterization, and X-ray crystallography to translate human RSV F stabilization into the bovine context,” the authors wrote. “A 'DS2' version of bovine respiratory syncytial virus F with subunits covalently fused, fusion peptide removed, and pre-fusion conformation stabilized by cavity-filling mutations and intra- and inter-protomer disulfides was recognized by pre-fusion-specific antibodies, AM14, D25, and MPE8, and elicited bovine respiratory syncytial virus-neutralizing titers in calves >100-fold higher than those elicited by post-fusion F.”
The investigators immunized five 3- to 6-week-old calves with the pre-F protein via two injections 4 weeks apart. They vaccinated another five calves with a post-F protein, while the third group of five calves received two placebo injections of saline. Four weeks after the second immunization, investigators infected all three groups with RSV. The calves vaccinated with the pre-F protein had high levels of neutralizing antibodies (more than 100-fold higher than those that received the post-F protein), and four of five were protected from RSV viral replication in the upper and lower respiratory tracts. In contrast, RSV was detected in all calves immunized with either the post-F protein or placebo.
“Our results demonstrate proof-of-concept that DS2-stabilized RSV F immunogens can induce highly protective immunity from RSV in a native host with implications for the efficacy of prefusion-stabilized F vaccines in humans and the prevention of bovine respiratory syncytial virus in calves,” the authors concluded.