Phase 1 Evaluation of Intranasal Virosomal Influenza Vaccine with and withoutEscherichia coliHeat-Labile Toxin in Adult Volunteers

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Abstract
Virosomal vaccines were prepared by extracting hemagglutinin (HA) and neuraminidase from influenza virus and incorporating it in the membranes of liposomes composed of phosphatidylcholine. Two intranasal spray vaccine series were prepared: one series comprised 7.5 μg of HA of each of three strains recommended by the World Health Organization and 1 μg ofEscherichia coliheat-labile toxin (HLT), and the other contained the HA without HLT. In addition, a third vaccine preparation contained 15 μg of HA and 2 μg of HLT. The parenteral virosomal vaccine contained 15 μg of HA without additional adjuvant. The immunogenicity of a single spray vaccination (15 μg of HA and 2 μg of HLT) was compared with that of two vaccinations (7.5 μg of HA with or without 1 μg of HLT) with an interval of 1 week in 60 healthy working adults. Twenty volunteers received one parenteral virosomal vaccine. Two nasal spray vaccinations with HLT-adjuvanted virosomal influenza vaccine induced a humoral immune response which was comparable to that with a single parenteral vaccination. A significantly higher induction of influenza virus-specific immunoglobulin A was noted in the saliva after two nasal applications. The immune response after a single spray vaccination was significantly lower. It could be shown that the use of HLT as a mucosal adjuvant is necessary to obtain a humoral immune response comparable to that with parenteral vaccination. All vaccines were well tolerated.