Abstract
BackgroundRespiratory syncytial virus (RSV) is a primary cause of serious lower respiratory tract illness for which there is still no safe and effective vaccine available. Using reverse genetics, recombinant (r)RSV and an rRSV lacking the G gene (ΔG) were constructed based on a clinical RSV isolate (strain 98-25147-X).ResultsGrowth of both recombinant viruses was equivalent to that of wild type virus in Vero cells, but was reduced in human epithelial cells like Hep-2. Replication in cotton rat lungs could not be detected for ΔG, while rRSV was 100-fold attenuated compared to wild type virus. Upon single dose intranasal administration in cotton rats, both recombinant viruses developed high levels of neutralizing antibodies and conferred comparable long-lasting protection against RSV challenge; protection against replication in the lungs lasted at least 147 days and protection against pulmonary inflammation lasted at least 75 days.ConclusionCollectively, the data indicate that a single dose immunization with the highly attenuated ΔG as well as the attenuated rRSV conferred long term protection in the cotton rat against subsequent RSV challenge, without inducing vaccine enhanced pathology. Since ΔG is not likely to revert to a less attenuated phenotype, we plan to evaluate this deletion mutant further and to investigate its potential as a vaccine candidate against RSV infection.
Highlights
Respiratory syncytial virus (RSV) is a primary cause of serious lower respiratory tract illness for which there is still no safe and effective vaccine available
The RSV genome of rRSV-X and ΔG Clinical isolate 98-25147-X (RSV-X) was PCR amplified into six large fragments, followed by sequential ligation (Figure 1A)
A cDNA recombinant RSV mutant lacking the G gene was subsequently constructed by deletion of the G gene, including its gene-end and gene-start, from the full-length plasmid
Summary
Respiratory syncytial virus (RSV) is a primary cause of serious lower respiratory tract illness for which there is still no safe and effective vaccine available. RSV is the most important cause of serious respiratory tract disease for young infants and children, and for the elderly and immunocompromised persons. More than 50% of the children are infected within their first year of life. The clinical manifestations range from mild, common cold-like symptoms to more severe bronchiolitis and pneumonia. Clinical observations indicate that the first infection with RSV is generally the most severe, whereas subsequent infections tend to be increasingly milder [1]. RSV infection accounts for 40 - 45% of children hospitalized for bronchiolitis or lower respiratory tract disease [2].
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