Selection of influenza B virus recombinants and their testing in humans for attenuation and immunogenicity

Abstract

The selection of influenza B virus recombinants from plaques in bovine kidney cell monolayers is described. Two sets of recombinants were each derived from parents of high and low virulence for humans, respectively. Recombination frequency was apparently high, and reassortment of genes made it possible to obtain attenuated recombinants containing the surface antigens of the virulent parents. Attenuation and immunogenicity were demonstrated in a series of volunteer trials. However, technique proved less satisfactory than for influenza A viruses which periodically undergo antigenic shift and for which there is a wide choice of parent viruses with distinctive surface antigens. In our two influenza B recombinant series there was appreciable antigenic overlap in the neuraminidases of the parents, even though in both cases these were chronologically widely separated. Another marker used was comparative titer at 35 and 38 degrees C. In practice, technical problems might sometimes make it difficult to ensure rapid production of live influenza B vaccines by recombination.