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Identification of a Recombinant Live Attenuated Respiratory Syncytial Virus Vaccine Candidate That Is Highly Attenuated in Infants
Abstract
BACKGROUND: Recombination technology can be used to create live attenuated respiratory syncytial virus (RSV) vaccines that contain combinations of known attenuating mutations. METHODS: Two live attenuated, recombinantly derived RSV vaccine candidates, rA2cp248/404 Delta SH and rA2cp248/404/1030 Delta SH, were evaluated in 31 adults and in 95 children >/=6 months old. rA2cp248/404/1030 Delta SH was subsequently evaluated in 44 infants 1-2 months old. These vaccine candidates share 4 attenuating genetic elements and differ only in a missense mutation (1030) in the polymerase gene. RESULTS: Both vaccines were highly attenuated in adults and RSV-seropositive children and were well tolerated and immunogenic in RSV-seronegative children. Compared with that of rA2cp248/404 Delta SH, replication of rA2cp248/404/1030 Delta SH was restricted in RSV-seronegative children (mean peak titer, 10(4.3) vs. 10(2.5) plaque-forming units [pfu]/mL), indicating that the 1030 mutation had a potent attenuating effect. Although rA2cp248/404/1030 Delta SH was well tolerated in infants, only 44% of infants who received two 10(5.3)-pfu doses of vaccine had detectable antibody responses. However, replication after administration of the second dose was highly restricted, indicating that protective immunity was induced. At least 4 of 5 attenuating genetic elements were retained in recovered vaccine viruses. CONCLUSIONS: rA2cp248/404/1030 Delta SH is the first RSV vaccine candidate to be sufficiently attenuated in young infants. Additional studies are needed to determine whether rA2cp248/404/1030 Delta SH can induce protective immunity against wild-type RSV.
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KIM, H. W., CANCHOLA, J. G., BRANDT, C. D., PYLES, G., CHANOCK, R. M., JENSEN, K., & PARROTT, R. H. (1969) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a120955 · Cited by 1,981
Cited by
Nair, H., Nokes, D. J., Gessner, B. D., Dherani, M., Madhi, S. A., Singleton, R. J., O'Brien, K. L., Roca, A., Wright, P. F., Bruce, N., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60206-1 · Cited by 2,773
Self-citationEpidemiology of Human Metapneumovirus
Kahn, J. S. (2006) · Clinical Microbiology Reviews · doi:10.1128/cmr.00014-06 · Cited by 355
The role of viruses in acute exacerbations of asthma
Jackson, D. J., & Johnston, S. L. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2010.04.021 · Cited by 351
Viral Etiology of Severe Pneumonia Among Kenyan Infants and Children
Berkley, J. A. (2010) · JAMA · doi:10.1001/jama.2010.675 · Cited by 304
Graham, B. S. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00972.x · Cited by 239
Metadata
- Authors
- Karron, R. A., Wright, P. F., Belshe, R. B., Thumar, B., Casey, R., Newman, F., Polack, F. P., Randolph, V. B., Deatly, A., Hackell, J., Gruber, W., Murphy, B. R., & Collins, P. L.
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-04
- Volume
- 191
- Issue
- 7
- Pages
- 1093-1104
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- OpenAlex
- W2106450636
- Cited by
- 287
- References
- 1
- FWCI
- 13.74
- Type
- journal article
- Language
- en
- Open access
- closed
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- The paper
- Karron, R. A., Wright, P. F., Belshe, R. B., Thumar, B., Casey, R., Newman, F., Polack, F. P., Randolph, V. B., Deatly, A., Hackell, J., Gruber, W., Murphy, B. R., & Collins, P. L. (2005). Identification of a Recombinant Live Attenuated Respiratory Syncytial Virus Vaccine Candidate That Is Highly Attenuated in Infants. The Journal of Infectious Diseases. https://doi.org/10.1086/427813
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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