A novel type of influenza vaccine: safety and immunogenicity of
replication-deficient influenza virus created by deletion of the interferon
antagonist NS1.
Author(s): Wacheck V, Egorov A, Groiss F, Pfeiffer A, Fuereder T, Hoeflmayer D, Kundi M,
Popow-Kraupp T, Redlberger-Fritz M, Mueller CA, Cinatl J, Michaelis M, Geiler J,
Bergmann M, Romanova J, Roethl E, Morokutti A, Wolschek M, Ferko B, Seipelt J,
Dick-Gudenus R, Muster T.
Affiliation(s): Departments of Clinical Pharmacology, Medical University of Vienna, Vienna,
Austria.
Publication date & source: 2010, J Infect Dis. , 201(3):354-62
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 .
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