Pattern recognition receptor agonist-loaded nanoparticles trigger effective antiviral responses against bovine and human Respiratory Syncytial Virus in vitro and in a murine RSV model
Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B565
Abstract ID: 4629
Presenting Author:
Fabian E Diaz , Postdoctoral Research Associate at Iowa State Col. of Vet. Med.
Abstract:
Human and bovine respiratory syncytial virus (RSV) are major agents of respiratory disease in infants and calves, respectively. While a vaccine to prevent hRSV in infants is lacking, vaccines against bRSV have failed to reduce the incidence RSV in calves. We have developed a nanoparticle (NP) platform to deliver innate receptor agonists to the respiratory mucosa and increase disease resistance. Here, we evaluated the immunogenicity of several NPs and their efficacy in preventing RSV disease in rodents.
To evaluate wheter NPs triggered antiviral responses, BT and A549 cells were treated with NPs for 24h, then infected with bRSV (375 st.) or hRSV A/1997 to quantify infectious titers. In in vivo experiments, 6-8-wk old B6 mice received NPs (i.n.), and then lungs were collected after 72h for cytokine quantification. Groups of NP-treated mice were infected with hRSV, then euthanized two dpi to collect whole lung and quantify viral copies (N-hRSV/β-actin copies).
Nanoparticles containing TL2/7, TLR2/1 or TLR4 agonists were able to prime epithelial cells and reduce hRSV and bRSV infectious titers in vitro. Administration of NPs containing a TLR2/7 agonist reduced weight loss and viral loads (p<0.01) in RSV-infected mice, which was associated with increased lung IL-1β, IL-6 (p<0.01), and KC (p<0.001) levels at the time of infection. These results suggest that NPs efficiently prime human and bovine respiratory tract epithelial cells and trigger antiviral defenses in vitro and in vivo.
Pattern recognition receptor agonist-loaded nanoparticles trigger effective antiviral responses against bovine and human Respiratory Syncytial Virus in vitro and in a murine RSV model
Category
Poster and Podium (Block Symposium)