tetano
Editor, Senior Moderator
Antimicrob Agents Chemother. 2014 Dec 22. pii: AAC.04431-14. [Epub ahead of print]
[h=1]Sialic Acid-Binding Protein Sp2CBMTD Protects Mice Against Lethal Challenge with the Emerging A(H7N9) Influenza Virus.[/h] Govorkova EA[SUP]1[/SUP], Baranovich T[SUP]2[/SUP], Marathe BM[SUP]2[/SUP], Yang L[SUP]3[/SUP], Taylor MA[SUP]3[/SUP], Webster RG[SUP]2[/SUP], Taylor GL[SUP]3[/SUP], Connaris H[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Compounds that target the cellular factors essential for influenza virus replication represent an innovative approach to antiviral therapy. Sp2CBMTD is a genetically engineered multivalent protein that masks sialic acid-containing cellular receptors on the respiratory epithelium, which are recognized by influenza viruses. Here, we evaluated the antiviral potential of Sp2CBMTD against lethal infection of mice with an emerging A/Anhui/1/2013(H7N9) influenza virus and addressed the mechanistic basis of its activity in vivo. Sp2CBMTD was administered to mice intranasally as a single or repeated dose (0.1, 1, 10, or 100 μg) before (day -7, -3, or/and -1) or after (6 or 24 h) H7N9 virus inoculation. A single Sp2CBMTD dose (10 or 100 μg) protected 80% to 100% of mice when administered 7 days before the H7N9 lethal challenge. Repeated Sp2CBMTD administration conferred the highest protection, resulting in 100% survival of mice even at the lowest dose tested (0.1 μg). When treatment began 24 h after exposure to the H7N9 virus, a single administration of 100 μg Sp2CBMTD protected 40% of mice from death. Administration of Sp2CBMTD induced pulmonary expression of proinflammatory mediators (IL-6, IL-1β, RANTES, MCP-1, MIP-1α, IP-10) and recruited neutrophils to the respiratory tract before H7N9 virus infection, which resulted in less pronounced inflammation and rapid virus clearance from mouse lungs. Sp2CBMTD administration did not affect the virus-specific adaptive immune response, which was sufficient to protect against reinfection with a higher dose of homologous H7N9 virus or heterologous H5N1 virus. Thus, Sp2CBMTD was effective in preventing H7N9 infections in a lethal mouse model and holds promise as a prophylaxis option against zoonotic influenza viruses.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID: 25534734 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25534734
[h=1]Sialic Acid-Binding Protein Sp2CBMTD Protects Mice Against Lethal Challenge with the Emerging A(H7N9) Influenza Virus.[/h] Govorkova EA[SUP]1[/SUP], Baranovich T[SUP]2[/SUP], Marathe BM[SUP]2[/SUP], Yang L[SUP]3[/SUP], Taylor MA[SUP]3[/SUP], Webster RG[SUP]2[/SUP], Taylor GL[SUP]3[/SUP], Connaris H[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Compounds that target the cellular factors essential for influenza virus replication represent an innovative approach to antiviral therapy. Sp2CBMTD is a genetically engineered multivalent protein that masks sialic acid-containing cellular receptors on the respiratory epithelium, which are recognized by influenza viruses. Here, we evaluated the antiviral potential of Sp2CBMTD against lethal infection of mice with an emerging A/Anhui/1/2013(H7N9) influenza virus and addressed the mechanistic basis of its activity in vivo. Sp2CBMTD was administered to mice intranasally as a single or repeated dose (0.1, 1, 10, or 100 μg) before (day -7, -3, or/and -1) or after (6 or 24 h) H7N9 virus inoculation. A single Sp2CBMTD dose (10 or 100 μg) protected 80% to 100% of mice when administered 7 days before the H7N9 lethal challenge. Repeated Sp2CBMTD administration conferred the highest protection, resulting in 100% survival of mice even at the lowest dose tested (0.1 μg). When treatment began 24 h after exposure to the H7N9 virus, a single administration of 100 μg Sp2CBMTD protected 40% of mice from death. Administration of Sp2CBMTD induced pulmonary expression of proinflammatory mediators (IL-6, IL-1β, RANTES, MCP-1, MIP-1α, IP-10) and recruited neutrophils to the respiratory tract before H7N9 virus infection, which resulted in less pronounced inflammation and rapid virus clearance from mouse lungs. Sp2CBMTD administration did not affect the virus-specific adaptive immune response, which was sufficient to protect against reinfection with a higher dose of homologous H7N9 virus or heterologous H5N1 virus. Thus, Sp2CBMTD was effective in preventing H7N9 infections in a lethal mouse model and holds promise as a prophylaxis option against zoonotic influenza viruses.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID: 25534734 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25534734