|Mcgill, Jodi - Kansas State University|
|Kelly, Sean - Iowa State University|
|Kumar, Pankaj - Kansas State University|
|Speckhart, Savannah - Kansas State University|
|Haughney, Shannon - Iowa State University|
|Henningson, Jamie - Kansas State University|
|Narasimhan, Balaji - Iowa State University|
Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/1/2018
Publication Date: 2/14/2018
Citation: McGill, J.L., Kelly, S.M., Kumar, P., Speckhart, S., Haughney, S.L., Henningson, J., Narasimhan, B., Sacco, R.E. 2018. Efficacy of mucosal polyanhydride nanovaccine against respiratory syncytial virus infection in the neonatal calf. Scientific Reports. 8:3021. https://doi.org/10.1038/s41598-018-21292-2.
DOI: https://doi.org/10.1038/s41598-018-21292-2 Interpretive Summary: In this manuscript, we have developed and tested a new vaccine for a respiratory virus in calves. The disease in calves closely mimics that in humans with a related respiratory virus, so the studies conducted provide data that will also be useful in developing a new vaccine for use in humans. The vaccine developed uses a new method for delivery of proteins from the virus. The proteins are enclosed in small particles that can be delivered into the nasal passages. Our work shows that the vaccine induced an appropriate immune response and provided significant protection to the calves following exposure to the live virus. This work will be of interest to those studying respiratory infections and those developing new vaccines against these infections.
Technical Abstract: Human respiratory syncytial virus (HRSV) is a leading cause of severe acute lower respiratory tract infection in infants and children worldwide. Bovine RSV (BRSV) is closely related to HRSV and a significant cause of morbidity in young cattle. BRSV infection in calves displays many similarities to RSV infection in humans, including similar age dependency and disease pathogenesis. Polyanhydride nanoparticle-based vaccines (i.e., nanovaccines) have shown promise as adjuvants and vaccine delivery vehicles due to their ability to promote enhanced immunogenicity through the route of administration, provide sustained antigen exposure, and induce both antibody- and cell-mediated immunity. Here, we developed a novel, mucosal nanovaccine that encapsulates the post-fusion F and G glycoproteins from BRSV into polyanhydride nanoparticles and determined the efficacy of the vaccine against RSV infection using a neonatal calf model. Calves receiving the BRSV-F/G nanovaccine exhibited reduced pathology in the lungs, reduced viral burden, and decreased virus shedding compared to unvaccinated control calves, which correlated with BRSV-specific immune responses in the respiratory tract and peripheral blood. Our results indicate that the BRSV-F/G nanovaccine is highly immunogenic and, with optimization, has the potential to significantly reduce the disease burden associated with RSV infection in both humans and animals.