Intranasal treatment with a novel immunomodulator mediates innate immune protection against lethal pneumonia virus of mice

- P-I-P pre-treatment, consisting of poly(I:C), IDR peptide and PCEP, was tested in the context of PVM infection in mice.
- P-I-P confers complete protection against lethal PVM infection by reducing clinical signs and immunopathology.
- P-I-P minimizes viral titers in the lungs reduces the influx of neutrophils and eosinophils into the tissue.
- P-I-P induces early upregulation of genes involved in host defense without any observable adverse effects.
- Survivor mice were PVM negative, suggesting that P-I-P mediates the successfully clearance of the virus in vivo.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in infants and young children. There are no licensed RSV vaccines available, and the few treatment options for high-risk individuals are either extremely costly or cause severe side effects and toxicity. Immunomodulation mediated by a novel formulation consisting of the toll-like receptor 3 agonist poly(I:C), an innate defense regulator peptide and a polyphosphazene (P-I-P) was evaluated in the context of lethal infection with pneumonia virus of mice (PVM). Intranasal delivery of a single dose of P-I-P protected adult mice against PVM when given 24 h prior to challenge. These animals experienced minimal weight loss, no clinical disease, 100% survival, and reduced lung pathology. Similar clinical outcomes were observed in mice treated up to 3 days prior to infection. P-I-P pre-treatment induced early mRNA and protein expression of key chemokine and cytokine genes, reduced the recruitment of neutrophils and eosinophils, decreased virus titers in the lungs, and modulated the delayed exacerbated nature of PVM disease without any short-term side effects. On day 14 post-infection, P-I-P-treated mice were confirmed to be PVM-free. These results demonstrate the capacity of this formulation to prevent PVM and possibly other viral respiratory infections.