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 separately 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. 71:8973-8982, 1997; and this study). The resulting viruses, designated rA2 Delta NS2 and rA2 Delta SH, were administered to chimpanzees to evaluate their levels of attenuation and immunogenicity. Recombinant virus rA2 Delta NS2 replicated to moderate levels in the upper respiratory tract, was highly attenuated in the lower respiratory tract, and induced significant resistance to challenge with wild-type RSV. The replication of rA2 Delta SH virus was only moderately reduced in the lower, but not the upper, respiratory tract. However, chimpanzees infected with either virus developed significantly less rhinorrhea than those infected with wild-type RSV, These findings demonstrate that a recombinant RSV mutant lacking either the NS2 or SH gene is attenuated and indicate that these deletions may he useful as attenuating mutations in ne cv, live recombinant RSV vaccine candidates for both pediatric and elderly populations. The Delta SH mutation was incorporated into a recombinant form of the cpts248/404 vaccine candidate, was evaluated fur safety in seronegative chimpanzees, and can now be evaluated as a vaccine for humans.