608. Dose Escalation of Recombinant Adenovirus-Based Influenza Virus Vaccine Encoding the Full Length Hemagglutinin (HA) of the A/Vietnam/1203/2004 (H5N1) To Immunize Naïve and Ad-Immune Mice

The recent emergence of highly avian influenza virus (HPAI) strains in poultry and their subsequent transmission to humans in Southeast Asia have raised concerns about the potential pandemic spread of lethal disease. We previously showed that recombinant adenovirus-based influenza A virus vaccine directed against the hemagglutinin (HA) protein of the A/Vietnam/1203/2004 (H5N1) can induce a 100% protection, associated with a cellular and humoral immune response, of mice and poultry against the lethal H5N1 avian influenza virus infection. In the present study we used the adenovirus encoding the full-length HA to analyze the humoral immune response after different dose of recombinant adenovirus. In view of clinical trials of the adenovirus-based influenza virus vaccine we determined the minimal amount of recombinant adenoviruses to induce the required titer measured by hemagglutination inhibition test. Due to the high frequency of anti-adenoviral immunity in the human population the efficiency of recombinant adenovirus-based vaccines are limited. To test the efficiency of the recombinant adenovirus-based influenza virus vaccine in the presence of neutralizing anti-adenoviral antibodies, we injected human IgG, which contains anti-adenoviral antibodies at a physiological level, before immunization. The result showed that 5|[times]|108 virus particle per mouse was the minimal amount to induce appropriate titers of antibodies. However, the immunization in the presence of neutralizing anti- adenoviral antibodies could only induce according antibody titer if we immunized with 5|[times]|1010 virus particle per mouse. This result improves our knowledge of the efficiency of recombinant adenoviral- based vaccines in the physiological situation in humans and is important for the design of clinical trials.