A Novel Type of Influenza Vaccine: Safety and Immunogenicity of Replication-Deficient Influenza Virus Created by Deletion of the Interferon Antagonist NS1

作者：Wacheck Volker; Egorov Andrej; Groiss Franz; Pfeiffer Andrea; Fuereder Thorsten; Hoeflmayer Doris; Kundi Michael; Popow Kraupp Therese; Redlberger Fritz Monika; Mueller Christian A; Cinatl Jindrich; Michaelis Martin; Geiler Janina; Bergmann Michael; Romanova Julia; Roethl Elisabeth; Morokutti Alexander; Wolschek Markus; Ferko Boris; Seipelt Joachim; Dick Gudenus Rosmarie; Muster Thomas^*

来源：Journal of Infectious Diseases, 2010, 201(3): 354-362.

DOI：10.1086/649428

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 (Delta NS1-H1N1) in healthy volunteers.
Methods. Healthy seronegative adult volunteers were randomized to receive either a single intranasal dose of the Delta NS1-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) (recipients) n = 36 or placebo (n = 12 recipients).
Results. Intranasal vaccination with the replication-deficient Delta NS1-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.

• 出版日期2010-2-1
• 单位河北医科大学