New Generation Live Vaccines against Human Respiratory Syncytial Virus Designed by Reverse Genetics
- 1 August 2005
- journal article
- review article
- Published by American Thoracic Society in Proceedings of the American Thoracic Society
- Vol. 2 (2) , 166-173
- https://doi.org/10.1513/pats.200501-011aw
Abstract
Development of a live pediatric vaccine against human respiratory syncytial virus (RSV) is complicated by the need to immunize young infants and the difficulty in balancing attenuation and immunogenicity. The ability to introduce desired mutations into infectious virus by reverse genetics provides a method for identifying and designing highly defined attenuating mutations. These can be introduced in combinations as desired to achieve gradations of attenuation. Attenuation is based on several strategies: multiple independent temperature-sensitive point mutations in the polymerase, a temperature-sensitive point mutation in a transcription signal, a set of non–temperature-sensitive mutations involving several genes, deletion of a viral RNA synthesis regulatory protein, and deletion of viral IFN α/β antagonists. The genetic stability of the live vaccine can be increased by judicious choice of mutations. The virus also can be engineered to increase the level of expression of the protective antigens. Protective...Keywords
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