Recombinant respiratory syncytial virus bearing a deletion of either the NS2 or SH gene is attenuated in chimpanzees

The NS2 and SH genes of respiratory syncytial virus (RSV) have been separat ely deleted from a recombinant wild-type RSV strain, A2 (M. N. Teng and P. L. Collins, J. Virol. 73:466-473, 1998; A. Bukreyev et al., J. Virol. 71:89 73-8982, 1997; and this study). The resulting viruses, designated rA2 Delta NS2 and rA2 Delta SH, were administered to chimpanzees to evaluate their l evels of attenuation and immunogenicity. Recombinant virus rA2 Delta NS2 re plicated to moderate levels in the upper respiratory tract, was highly atte nuated in the lower respiratory tract, and induced significant resistance t o challenge with wild-type RSV. The replication of rA2 Delta SH virus was o nly moderately reduced in the lower, but not the upper, respiratory tract. However, chimpanzees infected with either virus developed significantly les s rhinorrhea than those infected with wild-type RSV, These findings demonst rate that a recombinant RSV mutant lacking either the NS2 or SH gene is att enuated and indicate that these deletions may he useful as attenuating muta tions in ne cv, live recombinant RSV vaccine candidates for both pediatric and elderly populations. The Delta SH mutation was incorporated into a reco mbinant form of the cpts248/404 vaccine candidate, was evaluated fur safety in seronegative chimpanzees, and can now be evaluated as a vaccine for hum ans.