Construction and biological characterization of artificial recombinants between a wild type flavivirus (Kunjin) and a live chimeric flavivirus vaccine (ChimeriVax-JE)
Autor(es): Pugachev, Konstantin V.; Schwaiger, Julia; Brown, Nathan; Zhang, Zhen-xi; Catalan, John; Mitchell, Frederick S.; Ocran, Simeon W.; Rumyantsev, Alexander A.; Khromykh, Alexander A.; Monath, Thomas P.; Guirakhoo, Farshad
Resumo: Although the theoretical concern of genetic recombination has been raised related to the use of live attenuated flavivirus vaccines [Seligman, Gould, Lancet 2004;363:20735], it has little foundation [e.g., Monath TP, Kanesa-Thasan N, Guirakhoo F, Pugachev K, Almond J, Lang J, et al. Vaccine 2005;23:29568]. 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/KUNprM-E and KUN/JEprM-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
Palavras-Chave: Flavivirus vaccine; Recombination; Attenuation; ChimeriVax
Imprenta: Vaccine, v. 25, n. 37-38, p. 6661-6671, 2007
Identificador do objeto digital: 10.1016/j.vaccine.2007.07.016
Descritores: Aedes aegypti - Neurovirulence
Data de publicação: 2007
