Abstract: A synthetic hemagglutinin (sHA) which represents the highest degree of conservation in the HA sequences of all Influenza B viruses (IVB) based on comprehensive bioinformatics analyses was cloned into an adenoviral vector. The recombinant adenovirus carrying the sHA gene was then delivered intransallyintranasally into DAB/2 mice. The animals were challenged with 5xLD50 influenza B viruses. We have found that the synthetic HA vaccines afford 100% protection against lethal challenge whereas 50% mice died in the control group. Furthermore, no virus was found in the lung of the vaccinated group while significant lung viruses were found in all mice of the controlled group. Consistent with the survival data and virus titre, severe pneumonia was found in all mice of the control group while no pathologic observation was made in animals receiving the vaccines.