title: Intranasal treatment with a novel immunomodulator mediates innate immune protection against lethal pneumonia virus of mice.
abstract: 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.
authors: Department of Microbiology and Immunology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, 107 Wiggins Road, S7N 5E5, Canada; Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, Saskatoon, Saskatchewan, 120 Veterinary Road, S7N 5E3, Canada.
authors: Elisa C
authors: EC
authors: Martinez
authors: Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, Saskatoon, Saskatchewan, 120 Veterinary Road, S7N 5E3, Canada.
authors: Ravendra
authors: R
authors: Garg
authors: Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, Saskatoon, Saskatchewan, 120 Veterinary Road, S7N 5E3, Canada.
authors: Pratima
authors: P
authors: Shrivastava
authors: Department of Veterinary Pathology, Western College of Veterinary Medicine (WCVM), University of Saskatchewan, Saskatoon, Saskatchewan, 52 Campus Drive, S7N 5B4, Canada.
authors: Susantha
authors: S
authors: Gomis
authors: Department of Microbiology and Immunology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, 107 Wiggins Road, S7N 5E5, Canada; Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, Saskatoon, Saskatchewan, 120 Veterinary Road, S7N 5E3, Canada. Electronic address: sylvia.vandenhurk@usask.ca.
authors: Sylvia
authors: S
authors: van Drunen Littel-van den Hurk
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D016207:Cytokines / Q000276:immunology; D007113:Immunity, Innate; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D029122:Murine pneumonia virus / Q000276:immunology*; D009943:Organophosphorus Compounds / Q000008:administration & dosage* / Q000276:immunology; D018186:Pneumovirus Infections / Q000276:immunology / Q000517:prevention & control*; D011070:Poly I-C / Q000008:administration & dosage* / Q000276:immunology; D011108:Polymers / Q000008:administration & dosage*; D051196:Toll-Like Receptor 3 / Q000819:agonists
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D007155:Immunologic Factors; D009943:Organophosphorus Compounds; D011108:Polymers; D051196:Toll-Like Receptor 3; C108974:poly(phosphazene); D011070:Poly I-C
keywords: Immunomodulators; Innate immunity; PVM; Protection; RSV