Efficacy of a mucosal, polyanhydride nanovaccine for use against respiratory syncytial virus infection in the neonatal calf

Authors: 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; Sacco, Randy

Submitted to: Nature Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/1/2017
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. Nature Scientific Reports. 8(1):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, disease pathogenesis, and innate and adaptive immune responses. Development of an efficacious vaccine for BRSV poses similar challenges to that faced for HRSV, particularly the need to immunize the very young, the presence of maternally-derived antibodies and the possibility for the development of vaccine-enhanced disease. The calf is therefore an ideal model for testing novel vaccine candidates, assessing virus-specific immunity and determining appropriate correlates of vaccine-induced protection from infection. Polyanhydride nanovaccines (i.e. nanoparticle-based vaccines) have shown promise as adjuvants and vaccine delivery vehicles in rodent models due to their ability to promote enhanced immunogenicity through both the route of administration and the ability to provide sustained antigen exposure. Here, we developed a novel, mucosal nanovaccine that encapsulates the post-fusion F and G glycoproteins from BRSV into copolymers of 1,6-bis-(p-carboxyphenoxy)hexane and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane; and determined the efficacy of the vaccine against RSV infection using our neonatal calf model. In vitro, the BRSV-F/G nanovaccine induced activation and cytokine secretion by monocyte-derived dendritic cells and alveolar macrophages. In vivo, calves receiving the BRSV-F/G nanovaccine exhibited reduced BRSV-associated pathology in the lungs, reduced viral burden and decreased virus shedding compared to unvaccinated control calves; which correlated with a significant, amnestic BRSV-specific IgA response in the respiratory tract, and virus-specific cellular responses in the peripheral blood and airways. Our results suggest that the RSV-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.