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Recombinant respiratory syncytial virus bearing a deletion of either the NS2 or SH gene is attenuated in chimpanzees
- Source :
- Journal of virology. 73(4)
- Publication Year :
- 1999
-
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 cpts 248/404 vaccine candidate, was evaluated for safety in seronegative chimpanzees, and can now be evaluated as a vaccine for humans.
- Subjects :
- Genes, Viral
Pan troglodytes
viruses
Immunology
Mutant
Molecular Sequence Data
DNA, Recombinant
Virulence
Respiratory Syncytial Virus Infections
Biology
Viral Nonstructural Proteins
Recombinant virus
medicine.disease_cause
Microbiology
Virus
law.invention
Viral Proteins
Viral Envelope Proteins
law
Virology
medicine
Animals
Mutation
HN Protein
Base Sequence
Immunogenicity
Respiratory Syncytial Viruses
medicine.anatomical_structure
Insect Science
Recombinant DNA
Pathogenesis and Immunity
Gene Deletion
Respiratory tract
Subjects
Details
- ISSN :
- 0022538X
- Volume :
- 73
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Journal of virology
- Accession number :
- edsair.doi.dedup.....b6f2b148b162c98ae2453d011bd26a72