@article{796c5ac098de4f7fbd6e8cc3f7f90082,
title = "Japanese encephalitis virus live-attenuated vaccine, Chinese strain SA14-14-2; adaptation to primary canine kidney cell cultures and preparation of a vaccine for human use",
abstract = "The Japanese encephalitis (JE) live-attenuated vaccine virus clone SA14-14-2 was adapted to grow in primary canine kidney (PCK) cell culture, and vaccine seeds and a first lot of vaccine were prepared in these cells. Characterization of the PCK-grown virus by various laboratory and animal tests indicated that passage in PCK did not result in detectable phenotypic or genome changes for this virus clone. Markers of attenuation included small plaque size, lack of intracerebral virulence for weanling mice, minimal neurovirulence for rhesus monkeys and a distinct nucleotide pattern compared to the parent SA14 non-attenuated virus. In addition, the seeds and vaccine were free of any detectable adventitious microbial agents that would render these materials unsafe for human immunization. Small-scale clinical trials of the JE SA14-14-2 PCK vaccine can now proceed to test the human safety of this product.",
author = "Eckels, {Kenneth H.} and Yu Yong-Xin and Dubois, {Doria R.} and Marchette, {Nyven J.} and Trent, {Dennis W.} and Johnson, {Anthony J.}",
note = "Funding Information: not uncommonY. ellow fever 17D vaccines trainalso was conductedin compliancwe ith the Animal Welfare containsa numbero f unique nucleotidews hen com- Act and other Federals tatuteas nd regulationrse lating pared to the parentA sibi strain1 3. Sequencingo f the to animalsa nd experimentisn volvinga nimals anadd - JE vaccinev irusg enomea ndp arentg enomew ill allow herest o principless tatedin the GuideJor the Carea nd futurea ssignmenotf basec hangesto structuraol r non- Useo f LaboratorAy nimalsN, IH publication8 5-23.Y u structuravli ral proteinsa nde ventuallcyo rrelatiown ith Yong-Xin was supportedb y RockefellerF oundation modificationos f replicativefu nctiont hat result in an Grant RF 86014, No. 6. The technicala ssistanceo f attenuatepdh enotypeL.a ck of temperature-dependent Robert L. Timchaka nd DavidA . Barvir is greatlya p-restrictiono f viral replicationd oesnot seemt o be im-preciatedT. he authorsa re also gratefutl o Dr Scott B. portant for the observeda nimal attenuationo f this Halsteadfo r reviewingt he manuscript. virus. Lack of thet s phenotypea,l sothe casef or yellow fever 17D vaccine,s uggestst hat some form of host restrictionh aso ccurredfo r thesev iruses.B oth of these virusesh ave similar historieso f extensivpea ssagein hosts and host tissue that are notp art oft he natural infectionc ycle. The mousei s very useful as an experimentaaln imal for JE viral encephalit2is. The JE SA1~-14-2v accine virus is not encephalitogeninic young mice inoculated i.c. while the parentS A14virus causesa lethal encephalitis. Higher passagein PCK cells does nost electf or virulencea, s the vaccinev irusa fterP CK passage1 5 did not cause sicknesso r death in anotherg roupof i.c.-inoculatedm ice. Peripheravl irulencew ith J]E virusesis hard to dem-onstratein eithers malla nimalso r in primatesA. s was showni n this study,l arged oseso f intracerebral-virulent SA14 virus did not causee ncephalitiisn monkeysw hen givens ubcutaneouslEyv. env iraemiac ouldn ot be dem-onstratedin these animals.T he mouse potencays say uses ana ugmentepde ripheraclh allengbe ytraumatizing the brain with sterile diluent. The sham intracerebral inoculationp robablya llowsp assageo f virus and infection in the brain which resultins encephalitiasn ddeath in thesea nimals. Neurovirulenctee stsi n monkeysa lso indicatedth at the vaccinvei rushad minimale ncephalitogenic potential. CNS diseasea longw ith histopathologcich angesin brain and spinal tissueso f JE parentv irus-inoculated monkeysw eretypical of other non-attenuatevdir uses of the JE virus complexo f the flaviviruse6s. Neuro-virulencet estingo f productions eedsor vaccinel ots of YF vaccineis requiredb y regulatorya uthoritietso prove safety. This standards hould apply to all live-attenuateJdE vaccinesin tendedfo r humanu se. The stabilitya nd lack of animalv irulencefo r the JE SA14-14-2v accinev irus after adaptationan d growthi n PCK cells makes this virus a prime candidatefo r JE vaccinationS. mall scaleh umant estingf or safetya nd immunogenicimtya ynow proceedfo r the new JE PCK vaccine.",
year = "1988",
month = dec,
doi = "10.1016/0264-410X(88)90103-X",
language = "English (US)",
volume = "6",
pages = "513--518",
journal = "Vaccine",
issn = "0264-410X",
publisher = "Elsevier Ltd",
number = "6",
}