?????? ?????????,???????,????,??,????,??????800????,??60??????????????ο?
????????????????????????????????У????á????ɡ??????????????????????????????????????????????????????????????

????????????????????????з????

?????????????? ??????2019-09-04

???????? ??????????????? (Japanese encephalitis, JE) ??????????????? (JEV) ??????????ó洫????????????, ??????????в??????????????????????????????????JEV???????????????????????, ?????????????????????, ?????????????????????????????JEV?????????, ???????, ?????????, ????????25%????, ??????Ч?????????????????, ????????????????????????????????JEV?????????????μ????????????, ?????????????????????, ????????????????????????о?, ?Щ?????????α?????JEV?????з???, ?????????λ???硢?????????????硢???????????????硢???λ???硢DNA????????????????????????????, ?????????????????????????????????????????????????????????????????????, ?????JEV??????????????·??????????????JEV??????????????з????, ????????????????Ч????JEV???????ο??????

???????????????????????; ???????; ??????; ??; ??????????; ??????????;

????Abstract????Japanese encephalitis (JE) is an acute zoonosis, and has the characteristic of infectious diseases in the central neural system (CNS) , which caused by Japanese encephalitis virus (JEV) and transmitted by mosquitoes.The pigs are important storage and increase host of JEV, and it was main origin of infection.JEV can cause pregnant sow abortion and boar testitis.Humans are the terminal host of JEV, especially children, and the mortality rate can reach 25% after infection.There are still no effective drugs for JEV.The expansions of the epidemic area of JE and the changes of dominant genotypes have brought new challenges to the prevention and control strategies of JEV.In recent years, with the development of genetic and protein engineering, as well as the researches on the molecular structure and function of viruses, more and more new technologies and methods have been applied to the researches of vaccine for JEV.As a result, genetically engineered subunit vaccine, virus-like particle vaccine, chimeric virus attenuated live vaccine, polypeptide vaccine and DNA vaccine have emerged at the historic moment.In the process of vaccine preparation, the production process of optimizing the culture mode, purifying virus antigen, applying new adjuvant and heat resistant protective agents are expected to provide a new research direction for improving the quality of JEV vaccine.The present situation and development of swine encephalitis vaccine strain were reviewed in this paper to provide references for the development of safer and more effective vaccines against JEV.

????Keyword????Japanese encephalitis virus (JEV) ; inactivated vaccine; live-attenuated vaccine; swine; virus-like particles; genetically engineered vaccine;

?????????????? (Japanese encephalitis, JE) ?????????? (Flaviridae) ??????? (Flavivirus) ??????????? (Japanese encephalitis virus, JEV) ????????ó洫??????????????????????????????[1]??JEV????????????????? (???????) ?г??????????JEV?????????????????????????????????, ??????????, ?????? (????????) ????????????????????????????????????????, ????????25%????????JEV????????y??, ?????????????????????????????????, ??????γ?“??-??-??”??????????????????????????????????????Ч??, ???????????????JEV????????, ??????JEV??????з??????????????, ????з???Ч??????JEV???????ж??????????????Ч????[2]????????????????????绫????????????з????????????????????, ?????????????????Ч????JEV???????ο??????

????1?? ??????JEV???绫????????

????JEV????5????????:?????????, ???????????????????????????????????5??????????з??;?????????????????????????????????;?й???坞?????????????????????;????????????????????????????????;????????????й?????????????;???????????????????????????????;?????????????????????????????????п???????绫???????:Nakayama??SA14-14-2??Beijing-3 (P3) ??Beijing-1 (P1) ???, ???JEV???????[3]??

????????????????????????з????

????Nakayama?? (?????) 1935???????????????????????????[3], ????????????????, ??С??????????????JEV?????????, ???????????????????????????Beijing-1 (P1) ??1949???????????????????????, ??Nakayama??????????????巴???Beijing-3 (P3) ??1949????????????????????????, ???ж?С?????, ????????, ?????????????巴??????SA14-14-2??1954?????????????????????????????, ?????11?????????????????????????????100??, ??????????????, ???1????С???????5?????????5-3??, ????????????????????′???5??, ????2?κ???, ???ж?С?????2???, ???????????, ????????????

????2?? JEV????????

??????, ????4?????????JEV????:??????????硢?????????????硢???????????????????????????????硣????????????????????????????????????????????硣

????2.1?? ???????????

????JEV?????????20????30??????????, ??????????JEV????????????Biken?????????JE-VAX?[4], ?????????Nakayama????, ?????

????????JEV P1???????????????????????翘???????, ??????к???????, ??????????????????P1???????Nakayama???????????????????????, ?????????????????????С?????????????硣???????????????, ????в??????????, ???δ???????á?

????1950??1951??, ?й???????????????????о???????????????JEV?????P1??, 1952??1959????????á?1968?????????????????????????????????P3??, 37 ??????2 d??32 ??????3 d, ?????, ????????????簲???????????????????, ?????????????

????2.2?? ???????JEV???????

???????????????????????, ?????????????????????Ρ??????????JEV????????????, ???????????????????????JEV?????????JEV?????????????JEV??????????????????????????????????????????????????????P1????????Vero??????JEV??????硣????, IC51?????Vero????????????????????????????SA14-14-2?????????[5], ?????SA14-14-2????PDK?????????????Vero????????????, ???E????????138??176λ???????, ??????IC51????[6]??IC51?????в????κ???????????????????????2009??????, IC51?????????????????????????????????????????????????????3???????? (IXIARO??JESPECT??JEEV) ??

????1968??, ?й??????????????????????????JEV??????? (??P3?????????????????, ??????????????????????) ??1968??2000??????????JEV???硣???????????????????????, ????????????????????????????????????????????????????????????????????????????JEV????, ?????????Ч????1998??, ????Vero??????????????P3???????????????????????????????, ??????SA14-14-2?????????????????

????2.3 ?????????JEV??????????

????1989??, Yu[7]?????JEV SA14-14-2???????, ??????????????????JEV??????????, ???й??????????С??????????JEV SA14-14-2??????????????????????????????, ??????????????, ?????????????ɡ?WHO???簲??????????SA14-14-2????????????????, ?????????????, ?????????????????????С???????????????1?κ?????????????????????巴?, ????Ч????, ?????????JEV SA14-14-2???????????????????????????, ??????????????????????SA14-14-2????????????JEV???й???????????????, ???????????????????????????????????Ρ???颟?????????????????????[8]??

????2.4 ??????JEV????

??????, ????????JEV?????????????????????????????????????????????????JEV HW1?????????С????, ?????????С???????????????, ????????????, ???????????黯??ɡ?????????????????????, ????????????????, ????г?????ú?????????????JEV SA-14-14-2????????????????????, ??????????, ???????????, ????????????ɡ??????????????????????????β????, ?????????

??????JEV??????? (GD??) ????????GD??, Vero????????????????????, ??????, ????С????????????????????, ??С?????????, ???ò???????????????顣??JEV?????? (????????, SA14-14-2??) ?????????????????????????SA14-14-2???????Vero???????????????????????????????, ????????Ч?????ò?????????????顣

????3?? JEV?????з????

????3.1?? ?????????λ????

????JEV????????C?????PrM?????E?????C??????JEV?????????;M??????????????????????????Э????, ??????????????к?????????;PrM??????M????????, ??δ??????????????, ???????????????з?????????á?E???????JEV???????????, ??JEV?????????, ???????????, ????????????????к????, ???????к???????????λ??, ?????????????????λ??[9]?????, ????JEV E??M?????о????????Ч??????????????????JEV???????????????塣

????Zhang??[10]???ù???????????????????JEV E????, ?????????JEV PrM??E???????????п??????????????pAc5.1/v5-His??, ???????????????????S2????, ?????????????????JEV E?????????, ??????鵰??????С???????С?????????????к???塣Hua??[11]???????????????JEV????????????BJ-ML????, ?????????JEV??????????????????????????, ???????????15??20 μg/mL, ?????????С??????????ζ???к????, ???????????100%?????, ????????????Ч??JEV???λ????????

????3.2?? ??????????????

?????????????? (VLP) ??????????????????????????????????????????????, ??????????????????, ????????????, ????????????????????????, ?????????????????????????????????????VLP?????????????????з????????С?

???????????[12]??JEV PrM??E??????????????ο????????????AcBacmid??, ???????鴩??????AcBac-prME??Lipofectine?鵼????Sf9???, ?????????????Ac-prME???ò?????Sf9????и?Ч???, ???γ???????????????ò???????????????С??????Ч???JEV?????????????, ????????100%, ???????????JEV???????????λ????????????De Wispelaere??[13]?????????JEV????PrM??E???????????????????TRIP????, ????JEV VLPs, ??С?????????????????Ч?????ζ???JEV?к????, ?????JEV????????????????????, ????, ??????????JEV?????????????к???巴???Matsuda??[14]????????????????????PrM??E???????????JEV-Nakayama???????????????? (NVLP) ????ò???????????????Bm-N????????????????????????????????JEV Nakayama-BmNPV (JEV-NNPV) ???????????????????????, 3 d????????е?NVLP?????????, ??????????????300??500 μg??E?????????, NVLP???????????????????????? (HA) ???????NVLP???????????к????????Ч???к?JEV Nakayama??Beijing-1???MUAR?????, ?????????????????????JEV, ????г?????????Ч??????????, JEV???????????????????????????????, Fan??[15]????????????JEV????????????????????, ??????????????????????VLP, ?γ???????????????????????????????????????, ?ò???????????JEV???????????????????????, ?ò????????????JEV???????????н??汣?????á?????ò?????????????JEV????????????, δ?????????????????, ???????????????????о?δ???????????, ?????ò?????????????Ч??????JEV??????????????????

????3.3 ??????????????????

?????????????????????滻??????????????, ??JEV???緢???????·????о?????, ?????????????YFV17D?????????Ч????????????, ????????????????ζ???к????[16]??Appaiahgari??[17]??JEV SA14-14-2??PrM??E?????滻???????17D??cDNA????λ??, ??????????17D???C?????????????????????????????????, ?????????—?????????? (YF-JE) , ??????Vero?????????, ?????????????ChimeriVax TM-JE, ???????С???????, ??????????;?????н??????????, ???????????????????????????ζ???к????, ???????90%??????????????5???????????б????????, ????80%?????????????2???????????б????????[18]??????, ????ι????и?ζ?????—???????????????????, ????и???ò???, ??????????????????????????????????崫?????????????[19]????????????????г?????????????, ?????????????????????????, ??????????[20]???????????????????????????

????3.4 ?????λ????

???????λ?????????????λ?????????ж????????????????????, ??Я????????????????????λ??????, ??????????????????MHC??????????, ????????Ч????, ???а????á?????????????Ч?????????????????JEV????????????????λ?????????????????, ???????????????????С??, ??????С???????????????????????????????, ??????????JEV??????б???????, ????о??????Ч??JEV?????μ??·????????????[21]??????????JEV E??????λ?????????????????X33 (pPICZ-MP) , ??????????λ??rMP;???????rMP????С????????????????????????????, ?????С????????????JEV?????????Щ?о????????JEV???λ????????????????·??

????3.5?? DNA????

????DNA??????????б??????????????????е????????????????, ???????????????, ?????????????????????????????, ?????????????????????????硣????DNA??????????????????????????????????, ???????????о???????????е?????DNA?????????H5??????????DNA???硢????????????? (WNV) ??????????????????????????????? (IHNV) ????[22]??Li??[23]????????JEV E?????DNA???????pCAG-JME????С???, ?????С????????????к????, ??????????????????????С?????100%???????á????DNA??????С????????Ч?????, ?????????????????????????????, ?о????????????????????????????????????????и??, ???紩?? (EP) ?????????????????雕?????????????????, ????????DNA???缴?????????????????EP????????Ч???????, ??????DNA????????????й???????????[24]??Ketloy??[25]????????????2??????DNA??????????????????? (2????????????????JEV???????? (PrM) ??????????????????????????, ?????????????????, ????????PCJEME??PNJEME) , ???????, ??????????????????????2??100??450 mg DNA???? (???3??) ??????1??????????????1??40??1??160, ?????????245 d????, ?????????DNA?????????????????????????????????????B??????????塣DNA????????????????????????????????????????, ??δ????????????????????????

????4?? JEV?????з????

????4.1?? ???????????

????4.1.1?? ?????????????

??????, ?????????JEV????????????????????, ????????????????????????????????????????, ????????????????????????????Ч???????????????????, ??????????????????[26]??JEV SA14-14-2???????BHK-21??????????????, ????????JEV??????ν??ж????????, ???JEV???, ?????JEV???硣????????[27]??Vero???????????300 L?????????, ????????????й???????5??6 d??, ?????????????, ???????滻??????, ????JEV???????й???????, ????????????, ??????????????????????????????, ?????????????????, ???????????μ????????????????????, ?????????????

????4.1.2?? ????????????

??????, ?????????????JEV???绐????????, ??????????????????????????г?????????, ????????????????????????????л????????, ??????????????????????????????????, ??????????????????????????????????????????????[28]??????????????????????????????????????????????, ?DNA?ι???????????????????????????????????, ????????????DNA?????, ???????????????????, ?????[29]????п????????????????????????, ??Ч????????DNA, ???????????DNA??????????????????????[30]???????????崿?????????????????????????????????й???, ???????????JEV?????Ч??, ???????JEV?????????????д??????????????????Ч?????????????[31]???CaptoCore700????????JEV?????????????????, ?????????С???????????????????????????, ??????????????64.48%??70.35%, ??????????????????????15%??????????300%, ????????Ч????

????4.1.3?? ????????

????????????????????????????????, ????????????????????????????????, ???????????????????????, ???????з???????????????á???????[32]??603?????Gel01??ISA206??IMS1313???????????????????SCYA201201??????????????????4??????????????, ??С????????п??????????ɡ???????????????С???????????????, ??????, Gel01???????????С???, ?????????, ??JEV??????100%, ???С????????????????????Ч????á????????[33]????????????MontanideTM Gel01 ST (Gel01 ST) ?????JEV??????Э?????С??????????????, ??????, Gel01 ST????????????????С???, ???4???????忹??????????????????, ????7??????С????100%?????????Ч????Gel01 ST ???????????????С?????????????, ?????JEV????????????????????

????4.1.4 ??????????????

???????????????????, ???????????????????o?????????????, ??????????????????????仯, ?????????????????????????????????????????2??8 ???????±???24????, Ч???????????, ?????37 ????????10 d????????????????????????????, ????????桢????????????????á???????[34]??????1????JEV??????????????????, ????????JEV?????粡??????, ???????????????硣????????????????, ???????, ???????????, ???????????????????Ч???????[35]?з????????????????????????, ?????????????, ???????Ч??????????в???????, 37 ?????????20 d, 2??8 ???????2??????, ??????????????????????????, ?????????????????????

????4.2?? ????????????о???????

??????????, JEV???????????????????????????????????JEV????????????????JEV??????——??????2009????JEV???[36]??1970???, ?й????е?JEV???????????, 1979???????????JEV???????????, ????JEV?????????????й??????????????[37,38,39]????, JEV?????缰????????????JEV??????????硣?о?????, JEV???????????????JEV????????????????, ?????о?????, JEV??????????????????????????Ч????????????, ???JEV???????????????????????2?η???, ????????????????2???????, ??????JEV?????????к???????????????????????[40,41]?????????????JEV????????????о??????????????

????1952????η????JEV?????????? (Muar??, ??????????????) ??δ????????, ??????2009????????????? (????) ?????? (????) , ?????????JEV??????μ????[42]????JEV?????????????????????????????????????????, ???????????????????????JEV?????????????????????÷?????? (???????????50%) ?????в??JEV??????????????????[43], ??????????м??

????5?? С ??

???????????????????JEV?????????????, ?????????Ч??JEV????????????????????????JEV???????????20????40?????????С?????????, ????Щ????????????????, ????2011??5??????á??????????????????????????????????????????????, ???????μ??????????, ?????, ?????????????????档?????????????????????, ????????????????????????о?, ?Щ???????????α?????JEV?????о???, ???????????????λ???硢?????????????硢?????????硢???λ???硢DNA??????????????????????о?, ??????????????о????, ???????????????????????JEV?????????罫???????????????????????????????, ?????????????????????????????????, ??????????????????????????????????????????????????JEV????????????????μ?????????????о???????????, ????????????????????Ч????????????????????

?????ο?????

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