2010
DOI: 10.1086/649428
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A Novel Type of Influenza Vaccine: Safety and Immunogenicity of Replication‐Deficient Influenza Virus Created by Deletion of the Interferon Antagonist NS1

Abstract: BACKGROUND. The nonstructural protein NS1 of influenza virus counteracts the interferon-mediated immune response of the host. By deleting the open reading frame of NS1, we have generated a novel type of influenza vaccine. We studied the safety and immunogenicity of an influenza strain lacking the NS1 gene (DeltaNS1-H1N1) in healthy volunteers. METHODS. Healthy seronegative adult volunteers were randomized to receive either a single intranasal dose of the DeltaNS1-H1N1 A/New Caledonia vaccine at 1 of 5 dose lev… Show more

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Cited by 116 publications
(87 citation statements)
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“…The current research data prove that the vector technology based on the modification of the NS segment of influenza virus enables the generation of highly immunogenic recombinant virus strains that express the foreign sequences from the NS1 reading frame [90][91][92][93][94][95][96]. Clinical trials showed that viruses with the modified NS gene are safe and highly immunogenic [97]. The single immunization of mice with the vector strain based on the influenza virus A that express HA2 segments of the A and B influenza viruses from the NS1 open reading frame ensures the protection of animals from death not only after being challenged with influenza A viruses of other subtypes, but also after infection with the influenza virus В/Lee/40 (unpublished results).…”
Section: Resultsmentioning
confidence: 79%
“…The current research data prove that the vector technology based on the modification of the NS segment of influenza virus enables the generation of highly immunogenic recombinant virus strains that express the foreign sequences from the NS1 reading frame [90][91][92][93][94][95][96]. Clinical trials showed that viruses with the modified NS gene are safe and highly immunogenic [97]. The single immunization of mice with the vector strain based on the influenza virus A that express HA2 segments of the A and B influenza viruses from the NS1 open reading frame ensures the protection of animals from death not only after being challenged with influenza A viruses of other subtypes, but also after infection with the influenza virus В/Lee/40 (unpublished results).…”
Section: Resultsmentioning
confidence: 79%
“…Engineered NS1 deletions or truncations previously described in the literature have mostly been aimed at the development of novel attenuated influenza vaccines (Ngunjiriet al, 2015;Pica et al, 2012;Wacheck et al, 2010). Previous studies developing the human H1N1 PR8 strain as an OV also utilized NS1 deletion or truncation to improve the selectivity of the virus to replicate in IFN-deficient tumour cells (Muster et al, 2004;Sturlan et al, 2010).…”
Section: Resultsmentioning
confidence: 99%
“…Human volunteer recipients of a monovalent NS1-deleted vaccine candidate produced both nasal wash and serum antibodies, with almost no viral shedding, and experienced local symptoms that did not differ from those experienced by placebo recipients. 57 Serum antibodies that were induced despite the intranasal route of administration also cross-neutralized antigenically distinct, heterovariant viruses. A trivalent formulation is under clinical evaluation.…”
Section: Live Attenuated Influenza Vaccinesmentioning
confidence: 99%
“…If NS1 function is abrogated or reduced, a greater host native immune response to vaccination leads to a more robust cellular and humoral immune response and inhibits replication of the NS1-mutated virus. [57][58][59] Limited replication attenuates the infection and, importantly from a clinical safety perspective, limits viral shedding and averts transmission of the vaccine virus with the potential for reassortment. Human volunteer recipients of a monovalent NS1-deleted vaccine candidate produced both nasal wash and serum antibodies, with almost no viral shedding, and experienced local symptoms that did not differ from those experienced by placebo recipients.…”
Section: Live Attenuated Influenza Vaccinesmentioning
confidence: 99%