A novel type of influenza vaccine: safety and immunogenicity of replication-deficient influenza virus created by deletion of the interferon antagonist NS1.

Wacheck, Volker, Egorov, Andrej, Groiss, Franz, Pfeiffer, Andrea, Fuereder, Thorsten, Hoeflmayer, Doris, Kundi, Michael, Popow-Kraupp, Therese, Redlberger-Fritz, Monika, Mueller, Christian A, and others. (2010) A novel type of influenza vaccine: safety and immunogenicity of replication-deficient influenza virus created by deletion of the interferon antagonist NS1. Journal of Infectious Diseases, 201 (3). pp. 354-62. ISSN 0022-1899. (doi:10.1086/649428) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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http://dx.doi.org/10.1086/649428

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 levels (6.4, 6.7, 7.0, 7.4, and 7.7 log(10) median tissue culture infective dose) (n = 36 recipients) or placebo (n = 12 recipients). RESULTS. Intranasal vaccination with the replication-deficient DeltaNS1-H1N1 vaccine was well tolerated. Rhinitis-like symptoms and headache were the most common adverse events identified during the 28-day observation period. Adverse events were similarly distributed between the treatment and placebo groups. Vaccine-specific local and serum antibodies were induced in a dose-dependent manner. In the highest dose group, vaccine-specific antibodies were detected in 10 of 12 volunteers. Importantly, the vaccine also induced neutralizing antibodies against heterologous drift variants. CONCLUSIONS. We show that vaccination with an influenza virus strain lacking the viral interferon antagonist NS1 induces statistically significant levels of strain-specific and cross-neutralizing antibodies despite the highly attenuated replication-deficient phenotype. Further studies are warranted to determine whether these results translate into protection from influenza virus infection. TRIAL REGISTRATION. ClinicalTrials.gov identifier: NCT00724997 .

Item Type: Article
DOI/Identification number: 10.1086/649428
Subjects: Q Science > QR Microbiology > QR180 Immunology
Q Science > QR Microbiology > QR355 Virology
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Martin Michaelis
Date Deposited: 05 Jun 2013 19:22 UTC
Last Modified: 29 May 2019 10:14 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/34069 (The current URI for this page, for reference purposes)
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