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Journal of Virology, April 1999, p. 3438-3442, Vol. 73, No. 4
0022-538X/99

Recombinant Respiratory Syncytial Virus Bearing a Deletion of either the NS2 or SH Gene Is Attenuated in Chimpanzees

Stephen S. Whitehead,1,* Alexander Bukreyev,1 Michael N. Teng,1 Cai-Yen Firestone,1 Marisa St. Claire,2 William R. Elkins,3 Peter L. Collins,1 and Brian R. Murphy1

Respiratory Viruses Section1 and Experimental Primate Virology Section,3 Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, and Bioqual, Inc., Rockville, Maryland 208502

Received 13 November 1998/Accepted 7 January 1999

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 rA2Delta NS2 and rA2Delta SH, were administered to chimpanzees to evaluate their levels of attenuation and immunogenicity. Recombinant virus rA2Delta 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 rA2Delta 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 be useful as attenuating mutations in new, 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 for safety in seronegative chimpanzees, and can now be evaluated as a vaccine for humans.

* Corresponding author. Mailing address: LID, NIAID, 7 Center Dr., MSC 0720, Bethesda, MD 20892-0720. Phone: (301) 496-4205. Fax: (301) 496-8312. E-mail: sswhitehead{at}nih.gov.

Journal of Virology, April 1999, p. 3438-3442, Vol. 73, No. 4
0022-538X/99


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