LIVE SUBGROUP-B RESPIRATORY SYNCYTIAL VIRUS-VACCINES THAT ARE ATTENUATED, GENETICALLY STABLE, AND IMMUNOGENIC IN RODENTS AND NONHUMAN-PRIMATES

Optimal immunization of neonates against disease caused by respiratory syncytial virus (RSV) probably will require multiple doses of a vacci ne containing viruses of both subgroups A and B, Live subgroup B RSV m utants were generated containing multiple attenuating mutations, ts (t emperature-sensitive) and non-ts (host range), that were introduced by prolonged passage in cell culture or by chemical mutagenesis, The col d-passaged (cp)-52 mutant was restricted in replication compared to wi ld type virus in rodents and nonhuman primates, In addition, the atten uation phenotype of cp-52 was stable after prolonged replication in im munosuppressed rodents, One or two ts mutations were then introduced i nto the cp-52 mutant to generate additional candidate vaccine strains that were more attenuated in vivo than the cp-52 parental virus, Tests in humans are being done to determine if one or more of the RSV B-1 m utants exhibit a satisfactory balance between attenuation and immunoge nicity.