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

Stephen S. Whitehead, Alexander Bukreyev, Michael N. Teng, Cai Yen Firestone, Marisa St Claire, William R. Elkins, Peter L. Collins, Brian R. Murphy

Research output: Contribution to journalArticle

169 Citations (Scopus)

Abstract

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 rA2ΔNS2 and rA2ΔSH, were administered to chimpanzees to evaluate their levels of attenuation and immunogenicity. Recombinant virus rA2ΔNS2 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 rA2ΔSH 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 ΔSH 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.

Original languageEnglish (US)
Pages (from-to)3438-3442
Number of pages5
JournalJournal of Virology
Volume73
Issue number4
StatePublished - Apr 1999
Externally publishedYes

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Respiratory Syncytial Viruses
Pan troglodytes
viruses
Respiratory System
Genes
Viruses
genes
respiratory system
Vaccines
Respiratory Syncytial Virus Vaccines
Mutation
Synthetic Vaccines
vaccines
Virus Replication
varespladib methyl
mutation
Pediatrics
Safety
induced resistance
virus replication

ASJC Scopus subject areas

  • Immunology

Cite this

Whitehead, S. S., Bukreyev, A., Teng, M. N., Firestone, C. Y., Claire, M. S., Elkins, W. R., ... Murphy, B. R. (1999). Recombinant respiratory syncytial virus bearing a deletion of either the NS2 or SH gene is attenuated in chimpanzees. Journal of Virology, 73(4), 3438-3442.

Recombinant respiratory syncytial virus bearing a deletion of either the NS2 or SH gene is attenuated in chimpanzees. / Whitehead, Stephen S.; Bukreyev, Alexander; Teng, Michael N.; Firestone, Cai Yen; Claire, Marisa St; Elkins, William R.; Collins, Peter L.; Murphy, Brian R.

In: Journal of Virology, Vol. 73, No. 4, 04.1999, p. 3438-3442.

Research output: Contribution to journalArticle

Whitehead, SS, Bukreyev, A, Teng, MN, Firestone, CY, Claire, MS, Elkins, WR, Collins, PL & Murphy, BR 1999, 'Recombinant respiratory syncytial virus bearing a deletion of either the NS2 or SH gene is attenuated in chimpanzees', Journal of Virology, vol. 73, no. 4, pp. 3438-3442.
Whitehead, Stephen S. ; Bukreyev, Alexander ; Teng, Michael N. ; Firestone, Cai Yen ; Claire, Marisa St ; Elkins, William R. ; Collins, Peter L. ; Murphy, Brian R. / Recombinant respiratory syncytial virus bearing a deletion of either the NS2 or SH gene is attenuated in chimpanzees. In: Journal of Virology. 1999 ; Vol. 73, No. 4. pp. 3438-3442.
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