P0386 Oral adenovirus-based quadrivalent protects from lethal challenge with a H5N1 influenza ( H5N1) Roberto Mateo*1, Jonathan Lindbloom1, Christina Joyce1, Keith Gottlieb1, Sean Tucker1

1 Vaxart, Inc, South San Francisco, United States Background: H5N1 influenza is highly pathogenic and found in multiple species. Given the high mortality rate in , the global spread of H5N1 influenza is considered a significant threat. Current seasonal are not antigenically matched to provide H5N1 protection. Vaxart’s adenovirus-based oral tablet seasonal , previously tested in humans, may protect through different mechanisms than injectable vaccines that require a close vaccine match. Here, an H5N1 challenge study compares the efficacy of the oral and injectable flu vaccine approaches. Materials/Methods: Four adenovirus-based constructs expressing influenza HA matched to the individual components of the quadrivalent vaccine Fluzone were created. The four constructs were blended together in a liquid volume (4xAd-HA) and administered endoscopically to the ferret intestine (simulating oral enteric tablet delivery) on days 0 and 28. Two groups received either low or high dose levels of 1x1010 IU and 1x1011 IU per vaccine component, respectively. Two comparator groups received either PBS given by endoscope or Fluzone (QIV) given by . Each group had 8 animals. After 56 days, animals were intranasally inoculated with H5N1 virus (A/VN/1203/2004) and monitored daily for temperature, weight and survival. Serum samples were collected pre and post- to evaluate titers. Results: Animals in the PBS control group succumbed to virus-associated with 75% dying within 15 days after challenge. Animals vaccinated with QIV had a 38% death rate. Remarkably, all animals immunized with the higher dose of 4xAd-HA survived the heterologous H5N1 challenge. The HAI and total IgG ELISA titers against vaccine-matched strains of influenza A and B for the 4xAd-HA groups were higher than those generated in QIV and PBS-treated groups. Animals vaccinated with the high dose 4xAd-HA were 100% protected and maintained their weight and temperature post-challenge. Most PBS-treated animals lost weight and succumbed to the disease and QIV-immunized animals experienced significant weight and body temperature fluctuations. Conclusions: Vaxart’s oral seasonal vaccine conferred 100% protection against H5N1 disease and prevented associated weight loss and temperature changes. The immune mechanisms responsible for this significant cross- protection are currently being explored in clinical trials and additional ferret challenge studies.

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