Project Number: 5030-32000-117-073-R
Project Type: Reimbursable Cooperative Agreement
Start Date: Oct 1, 2020
End Date: Jul 31, 2022
In a project currently funded by the NIH, we have recently developed the first generation of a novel, polyanhydride nanoparticle-based vaccine encapsulating the post-fusion F protein and the G protein from BRSV. We have determined that a single intranasal immunization with the BRSV-F/G nanovaccine induces cellular and humoral immunity in the respiratory tract, reduces virus-associated pathology and decreases the incidence of virus shedding in neonatal calves. Our initial success with the preliminary formulation of the BRSV-F/G nano-vaccine provides compelling evidence to pursue the nanovaccine platform for use against RSV. However, the single-dose BRSV-F/G nanovaccine did not induce sterilizing immunity or provide 100% protection from dis-ease pathology, and there is a significant need to further optimize our approach. Here, we propose to use our innovative model of BRSV infection in calves, to further develop the novel, polyanhydride-based nanoparticle platform, which we believe has significant potential to protect from RSV infection in both humans and animals. Our central hypothesis is that use of a mucosal, TLR-agonist encapsulating, pre-fusion F based polyanhydride nanovaccine will promote long-term protection from RSV infection.
Aim 1. Determine the efficacy and immunogenicity of mucosal, polyanhydride nanovaccine incorporat-ing CpG and the post-fusion F and G nanovaccine for protecting against RSV infection in neonatal calves. Aim 2. Determine the immunogenicity and efficacy of a mucosal, pre-fusion F protein based polyanhy-dride nanovaccine for protecting neonatal calves against RSV infection.