Investigetion into the attenuation of influenza viruses by serial passage

For vaccination live viruses are better than dead ones, but live influenza vaccines are difficult to prepare. One influenza A(2) and two influenza B viruses were passed in series in embryonated eggs. At several stages of their passage they were inoculated into volunteers, and their effects assessed by virus isolations, antibody rises, and clinical reactions. The A(2) virus and one of the influenza B viruses, both of which had grown readily in embryonated eggs on first isolation, continued to induce human infections and clinical reactions after 30 egg passes. The other influenza B virus acquired enhanced human pathogenicity after three passages from man to man. After adaptation to eggs in which it at first grew reluctantly, its human virulence was appreciably reduced. It underwent no further change during a total of 20 egg passes. There was little convincing evidence of an increased incidence of clinical reactions during the winter seasons, but the numbers of volunteers were too small to draw definite conclusions.