Abstract：
:Although the theoretical concern of genetic recombination has been raised related to the use of live attenuated flavivirus vaccines [Seligman, Gould, Lancet 2004;363:2073-5], it has little foundation [e.g., Monath TP, Kanesa-Thasan N, Guirakhoo F, Pugachev K, Almond J, Lang J, et al. Vaccine 2005;23:2956-8]. To investigate biological effects of recombination between a chimeric yellow fever (YF) 17D/Japanese encephalitis (JE) vaccine virus (ChimeriVax-JE) and a wild-type flavivirus Kunjin (KUN-cDNA), the prM-E envelope protein genes were swapped between the two viruses, resulting in new YF 17D/KUN(prM-E) and KUN/JE(prM-E) chimeras. The prM-E genes are easily exchangeable between flavivirues, and thus the exchange was expected to yield the most replication-competent chimeras, while other rationally designed recombinants would be more likely to be crippled or non-viable. The new chimeras proved highly attenuated in comparison with the KUN-cDNA parent, as judged by plaque size and growth kinetics in cell culture, low viremia in hamsters, and reduced neurovirulence/neuroinvasiveness in mice. These data provide strong experimental evidence that the potential of recombinants, should they ever emerge, to cause disease or spread (compete in nature with wild-type flaviviruses) would be indeed extremely low.
journal_name
Vaccinejournal_title
Vaccineauthors
Pugachev KV,Schwaiger J,Brown N,Zhang ZX,Catalan J,Mitchell FS,Ocran SW,Rumyantsev AA,Khromykh AA,Monath TP,Guirakhoo Fdoi
10.1016/j.vaccine.2007.07.016subject
Has Abstractpub_date
2007-09-17 00:00:00pages
6661-71issue
37-38eissn
0264-410Xissn
1873-2518pii
S0264-410X(07)00797-9journal_volume
25pub_type
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