The live attenuated subgroup B respiratory syncytial virus vaccine candidate RSV 2B33F is attenuated and immunogenic in chimpanzees, but exhibits partial loss of the ts phenotype following replication in vivo

The cold-adapted (ca), temperature-sensitive (ts) respiratory syncytial vir us (RSV) subgroup B vaccine candidate, designated RSV 2B33F, was found prev iously to be restricted in replication, immunogenic, and protective against wild-type (wt) virus challenge in rodents and African green monkeys. We so ught to investigate the level of attenuation, immunogenicity and genetic st ability of this vaccine candidate in seronegative chimpanzees. The 2B33F va ccine candidate was attenuated in chimpanzees and manifested a ten- and 100 0-fold restriction in replication in the upper and lower respiratory tracts respectively, compared with its wt RSV 2B parent virus. Despite this atten uation, chimpanzees immunized with RSV 2B33F were completely resistant to r espiratory tract disease and virus replication upon challenge with wt virus . The ts phenotype of the RSV 2B33F mutant exhibited some alteration during replication in vivo in three of four chimpanzees tested. Virus present in nasopharyngeal swab or tracheal lavage secretions of these three chimpanzee s was biologically cloned by plaque passage in Vero cells at permissive tem perature. The plaque progeny retained the ts phenotype, but uniformly produ ced plaques at 39 and 40 degrees C to a level intermediate between that of the 2B33F input virus and the 2B wt parent virus, indicating that partial l oss of the level of temperature sensitivity occurred following replication in vivo. The implications of these findings for RSV vaccine development are discussed. (C) 1999 Elsevier Science B.V. All rights reserved.