¡¡¡¡Õª Òª£º¡¡µÇ¸ïÈÈ(dengue fever)ÊÇÒ»ÖÖÓÉЯ´øµÇ¸ï²¡¶¾(dengue virus)µÄÎÃý¶£Ò§ÒýÆðµÄ¼±ÐÔ´«È¾ÐÔ¼²²¡¡£µÇ¸ïÈÈÒѾÔÚ100¶à¸ö¹ú¼ÒºÍµØÇøÁ÷ÐÐ,ÿÄêÔ¼ÓÐ3.9ÒÚÈ˸ÐȾ¡£2019Äê³õÊÀ½çÎÀÉú×éÖ¯(WHO)½«µÇ¸ï²¡¶¾ÒýÆðµÄµÇ¸ïÈȼ²²¡ÁÐΪ2019ÄêÈ«Çò½¡¿µÃæÁÙµÄÊ®´óÍþв֮һ¡£×Ô2019ÄêÄê³õÖÁ8Ôµ×,µÇ¸ïÈÈÒßÇéÒÑÔÚÈ«Çò20¶à¸ö¹ú¼ÒºÍµØÇø±©·¢,¸ÐȾÈËÊý³¬¹ý150ÍòÀý¡£µÇ¸ïÈÈ·¢²¡»úÖÆÉв»Ã÷È·,ÇÒÆù½ñûÓÐÌØЧҩ,ÒßÃçÔ¤·ÀºÍÎÃý¿ØÖÆÊǶôÖƵǸﲡ¶¾´«²¥µÄÓÐЧÊֶΡ£±¾ÎIJûÊö½üÄêÀ´µÇ¸ïÒßÃçµÄÑз¢ºÍÎÃý¿ØÖÆ·½ÃæµÄ×îнøÕ¹,Ìá³öδÀ´µÇ¸ïÒßÃç·¢Õ¹ÓÐÍûÔÚÓÅÊÆ¿¹ÔÖØÐÂ×éºÏ¡¢¿ª·¢ÐÂÐ͵ÝËÍϵͳµÈ·½Ãæ»ñµÃÍ»ÆÆ,»ùÒò±à¼µÈÐÂÐͼ¼ÊõµÄÐËÆð¿É´Ù½øÎÃý¿ØÖÆÑо¿µÄ·¢Õ¹¡£
¡¡¡¡¹Ø¼ü´Ê£º¡¡µÇ¸ïÈÈ; µÇ¸ï²¡¶¾; ÎÃý½é; ÒßÃç; Ô¤·ÀÓë¿ØÖÆ;
¡¡¡¡Abstract£º¡¡Dengue fever is an acute infectious disease caused by mosquito vector bites carrying dengue virus. Dengue fever has been prevalent in more than 100 countries and regions, with about 390 million people infected each year. In early 2019, the World Health Organization(WHO)listed dengue fever caused by dengue virus as one of the top 10 threats to global health in 2019. From the beginning of 2019 to the end of August, dengue fever outbreaks have occurred in more than 20 countries and regions around the world, with more than 1.5 million cases of infection. Up to date, it is not clear about the pathogenesis of dengue fever, and there is no target drug. Vaccine prevention and mosquito vector control are effective means to control the transmission of the virus. Vaccine prevention and mosquito vector control are effective means to curb the spread of dengue virus. This article reviews the latest progress in the research and development of dengue vaccine and mosquito vector control in recent years. The development of dengue vaccine in the future is expected to make breakthroughs in the reassembly of dominant antigens and the development of new delivery systems. The rise of new technologies such as gene editing will promote the development of mosquito vector control research.
¡¡¡¡Keyword£º¡¡dengue fever; dengue virus; mosquito vector; vaccine; prevention and control;
¡¡¡¡µÇ¸ïÈÈ(dengue fever,DF)ÊÇÒ»ÖÖÓÉЯ´øµÇ¸ï²¡¶¾(dengue virus,DV)µÄÎÃý¶£Ò§ÒýÆðµÄ¼±ÐÔ´«È¾ÐÔ¼²²¡¡£Æ䲡ÔÌåµÇ¸ï²¡¶¾ÊôÓڻƲ¡¶¾¿ÆÖеĻƲ¡¶¾Êô,ÓÉ°£¼°ÒÁÎÃ(aedes aegypti)»ò°×ÎÆÒÁÎÃ(aedes albopictus)Я´ø´«²¥¡£ÓÉÓÚÎÃý×ÌÉúѸËÙ,µÇ¸ïÈȵĴ«²¥Òò´ËҲѸËÙ¶ø¹ã·º[1]¡£¾ÝÊÀ½çÎÀÉú×éÖ¯(WHO)ͳ¼ÆÏÔʾ,µÇ¸ïÈÈÄ¿Ç°ÒѾÔÚ100¶à¸ö¹ú¼ÒºÍµØÇøÁ÷ÐÐ,È«ÇòÓÐ25¡«30ÒÚÈËÉú»îÔڵǸïÈÈÁ÷ÐÐÇøÓò,ÿÄêÔ¼ÓÐ3.9ÒÚÈ˸ÐȾ[2]¡£¶àÊýÇé¿öÏÂ,µÇ¸ï²¡¶¾¸ÐȾÒýÆðµÄµÇ¸ïÈÈÁÙ´²Ö¢×´½ÏÇá,Ë没³Ì½øÕ¹¿É×ÔÐÐȬÓú,µ«Ò²ÓÐÉÙÊý¸ÐȾÕß²¡³ÌÖð½¥¼ÓÖØ,·¢Õ¹ÎªµÇ¸ï³öѪÈÈ(dengue hemorrheagic fever,DHF)¼°µÇ¸ïÐÝ¿Ë×ÛºÏÕ÷(dengue shock syndrome,DSS),ºóÕß²¡ËÀÂʼ«¸ß[3]¡£µÇ¸ïÐÝ¿Ë×ÛºÏÕ÷³ýÁ˱íÏÖ³öÑÏÖصijöѪÇãÏòºÍ³öѪÐÔÐÝ¿ËÖ®Íâ,Ö÷Òª»¹¿É±íÏÖΪ¾çÁÒÍ·Í´¡¢¶ñÐÄ¡¢Å»Í¡¢ÒâʶÕÏ°¡¢¾±Ç¿Ö±µÈ,¶àÊý»¼Õß×îÖÕÒòÖÐÊàÐÔºôÎüË¥½ßºÍ³öѪÐÔÐÝ¿ËÔÚ24 hÄÚËÀÍö¡£½ü10ÄêÀ´,µÇ¸ïÈÈÔÚÈ«ÊÀ½ç·¶Î§Á÷ÐÐÓмӾçÇ÷ÊÆ,ÒѾ³ÉΪȫÇòÐÔ¹«¹²ÎÀÉúÄÑÌâ[4]¡£
¡¡¡¡1¡¢ µÇ¸ïÈÈÒѳÉΪȫÇò½¡¿µÖØÒªÍþв
¡¡¡¡2019Äê³õWHO½«µÇ¸ï²¡¶¾ÒýÆðµÄµÇ¸ïÈȼ²²¡ÁÐΪ2019ÄêÈ«Çò½¡¿µÃæÁÙµÄÊ®´óÍþв֮һ¡£×Ô2019ÄêÄê³õÖÁ8Ôµ×,µÇ¸ïÈÈÒßÇéÒÑÔÚÈ«Çò20¶à¸ö¹ú¼ÒºÍµØÇøƵƵ±©·¢,ÆäÖÐÒÔ·ÆÂɱö¡¢Ô½ÄÏ¡¢Ì©¹ú¡¢ÂíÀ´Î÷Ñǵȶ«ÄÏÑǹú¼ÒºÍÄÏÃÀÖ޵İÍÎ÷ÒßÇé×îΪÑÏÖØ;È«ÇòµÇ¸ïÈȲ¡Àý×ÜÊýÒѳ¬¹ý150ÍòÀý,ÒýÆðÈ«Çò¸÷½çÈËÊ¿¹ã·º¹Ø×¢[3]¡£ÒÔ²¿·Ö¶«ÄÏÑǹú¼ÒΪÀý,·ÆÂɱöÔÚ2019Äê6ÔÂ15ÈÕ±¨¸æµÄµÇ¸ïÈȲ¡ÀýΪ77 040Àý,¶øÔÚ2019Äê8ÔÂ3ÈÕÒѼ±¾çÉÏÉýÖÁ188 562Àý,Ç°ºóÏà¸ô²»µ½2¸öÔÂʱ¼ä,²¢ÇÒÓÖÔÚ2ÖܺóÍ»ÆÆÁË20ÍòÀý(WHO¹Ù·½Êý¾ÝÏÔʾ´ïµ½229 736Àý),ËÀÍöÈËÊý958ÈË¡£½ØÖÁ2019Äê8ÔÂ17ÈÕ,ÂíÀ´Î÷ÑǵǸïÈȲ¡ÀýÀۼƳ¬8.5ÍòÀý,ÊÇ2018ÄêͬÆÚ2±¶ÒÔÉÏ,ÆäÖÐ121ÈËËÀÓڵǸïÈÈ;2019ÄêÉÏ°ëÄê,Ô½ÄϵĵǸïÈȲ¡ÀýÀۼƴï8.8ÍòÀý,½Ï2018ÄêͬÆÚÔö¼Ó2±¶ÒÔÉÏ,ÆäÖÐÖÁÉÙ6Àý»¼ÕßËÀÍö;2019Äê1ÔÂÖÁ7ÔÂ,¼íÆÒÕ¯Óг¬¹ý1.4ÍòÃû¶ùͯ¸ÐȾµÇ¸ïÈÈ¡£½ØÖÁ2019Äê7ÔÂ7ÈÕ,ÀÏÎÎÓг¬¹ý1.4ÍòÈ˸ÐȾµÇ¸ïÈÈ,31ÈËËÀÍö¡£×Ô2019ÄêÄê³õÖÁ8ÔÂ24ÈÕ,мÓÆÂÒ²·¢ÏÖÁË10 683ÀýµÇ¸ïÈȲ¡Àý,ÊÇ2018ÄêͬÆÚµÄ6±¶¡£
¡¡¡¡2¡¢ µÇ¸ïÈȵÄÔ¤·ÀÓëý½é¿ØÖÆ
¡¡¡¡2.1¡¢ µÇ¸ï²¡¶¾µÄ¿ÉÄÜÖ²¡»úÖÆ
¡¡¡¡µÇ¸ï²¡¶¾»ùÒò×éÈ«³¤Ô¼11 kb,Ϊµ¥Á´ÕýÁ´RNA²¡¶¾¡£´Ó5′¶Ë¿ªÊ¼ÒÀ´Î±àÂëÁË11¸öµ°°×,°üÀ¨4¸ö½á¹¹µ°°×(C¡¢PrM¡¢MºÍE)ºÍ7¸ö·Ç½á¹¹µ°°×(NS1¡¢NS2a¡¢NS2b¡¢NS3¡¢NS4a¡¢NS4bºÍNS5)¡£µÇ¸ï²¡¶¾¿ÅÁ£ÎªÇòÐÎ20ÃæÌå,Ö±¾¶Ô¼55 nm¡£²¡¶¾¿ÅÁ£Íâ±»Ö¬µ°°×°üĤ,²¢¾ßÓаüĤ´ÌÍ»¡£²¡¶¾°üĤµÄÍâ²ãº¬ÓаüĤµ°°×E,Äڲ㺬ÓÐĤµ°°×M¡£µÇ¸ï²¡¶¾ÒÀEµ°°×¿¹ÔÐÔ²»Í¬±»·ÖΪ4ÖÖѪÇåÐÍ,·Ö±ðΪDV1¡¢DV2¡¢DV3ºÍDV4¡£¸÷ѪÇåÐͲ¡¶¾Ö®¼ä¿¹ÔÐÔÓн»²æ,ÆäÖеǸﲡ¶¾2ÐͽÏÆäËû3ÖÖѪÇåÐͲîÒì×î´ó¡£
¡¡¡¡µÇ¸ïÈÈ·¢²¡»úÖÆÉв»Ã÷È·,Æù½ñÉÐÎÞÌØЧҩÎï,ÁÙ´²ÖÎÁÆÖ»ÄÜÒÔÖ§³ÖÖÎÁÆΪÖ÷¡£ÒÑÓеÄÁÙ´²×ª»¯Ò½Ñ§ºÍÏà¹ØÒßÃçÑо¿½ÒʾÆä¿ÉÄܵĻúÖÆ°üÀ¨¿¹ÌåÒÀÀµÔöÇ¿×÷ÓúÍϸ°ûÒò×ӷ籩×÷Óᣢ٠¿¹ÌåÒÀÀµÔöÇ¿(antibody dependent enhancement,ADE)×÷ÓÃ[5],ÒÑÓеÄÁÙ´²×ª»¯Ò½Ñ§Ñо¿Ö¤Êµ,µÇ¸ï²¡¶¾¸ÐȾºó²úÉúµÄ¿¹Ìå³ýÁ˾ßÓÐÖкÍ×÷ÓõÄÖкÍÐÔ¿¹Ìå,»¹ÓзÇÖкÍÐÔ¿¹Ìå¡£·ÇÖкÍÐÔ¿¹ÌåÔÚÒìÖÖѪÇåÐÍÔٴθÐȾÖÐÏÔ×ÅÔö¼Ó¡£Ò»·½Ãæ,ͨ¹ýÓ벡¶¾¿ÅÁ£Ïà½áºÏÐγɲ¡¶¾¿¹Ì帴ºÏÎï,²¢Í¨¹ý¿¹ÌåµÄFcÊÜÌå(FcR)½áºÏ½øÈëµ¥ºË-¾ÞÊÉϸ°û,ÔöÇ¿µÇ¸ï²¡¶¾¸ÐȾ,¾ÑªÒºÑ»·¼ÓÖØÈ«ÉíÐÔ¸ÐȾ¡£ÁíÒ»·½Ãæ,¸ÐȾµÄµ¥ºË-¾ÞÊÉϸ°û¾²¡¶¾¿ÅÁ£»ò²¡¶¾¿¹Ô¿¹Ì帴ºÏÎïµÈ´Ì¼¤,¿ÉÒÔÓÕµ¼¼¤»îÊÍ·Å´óÁ¿Ñ×ÐÔÒò×ÓºÍÇ÷»¯Òò×Ó,ÒýÆðÃÖÉ¢ÐÔѪ¹ÜÄÚÄýѪ(DIC)¡¢³öѪ¡¢Ðݿ˵ÈһϵÁв¡Àí¹ý³Ì[6]¡£ ¢Ú ϸ°ûÒò×ӷ籩(cytokine storm)[7,8],Ö¸»úÌå¸ÐȾµÇ¸ï²¡¶¾ºóÒýÆðÌåÒºÖжàÖÖϸ°ûÒò×ÓÈçTNF-α¡¢IL-1¡¢IL-6¡¢IL-12¡¢IFN-α¡¢IFN-β¡¢IFN-γ¡¢MCP-1ºÍIL-8µÈѸËÙ¡¢´óÁ¿²úÉúµÄÏÖÏó¡£ÕâÖÖÏÖÏóÔڵǸï³öѪÈȺ͵ǸïÐÝ¿Ë×ÛºÏÕ÷»¼ÕßÖзdz£³£¼û¡£ÒìÖÖѪÇåÐÍÔٴθÐȾÓÕ·¢½»²æ·´Ó¦ÐÔCD4+ϸ°û»î»¯,»ò¸¨Öú½»²æ·´Ó¦ÐÔCD8+ϸ°û¶¾ÐÔTÁÜ°Íϸ°û(cytotoxic lymphocyte,CTL)»î»¯¡£»î»¯µÄ²¡Àí·´Ó¦ÐÔTϸ°ûÊÍ·Å´óÁ¿Ñ×ÐÔϸ°ûÒò×ÓÈçIL-2¡¢IFN-γ¡¢×é°·¡¢¹ýÃôËØC3aºÍC5aµÈ,¼ÓÖصǸï³öѪÈȺ͵ǸïÐÝ¿Ë×ÛºÏÕ÷»¼ÕßÐÝ¿Ë¡¢Ñ»·Ë¥½ßºÍ³öѪµÈÖ¢×´¡£
¡¡¡¡2.2¡¢ µÇ¸ïÒßÃçÑо¿½øÕ¹
¡¡¡¡µÇ¸ïÈÈÆù½ñΪֹûÓÐÌØЧҩ,ÒßÃçÊǶôÖƲ¡¶¾¸ÐȾµÄ×îÓÐЧÊֶΡ£Ò»¸öÀíÏëµÄÒßÃçÓ¦µ±Äܹ»²úÉúÓÐЧµÄ±£»¤ÐÔÃâÒßÓ¦´ð,°üÀ¨ÌåÒºÃâÒߺÍ/»òϸ°ûÃâÒßÓ¦´ð¡£È»¶ø,ÕýÈçÇ°ÊöµÄ¿ÉÄÜÖ²¡»úÖÆÒÔ¼°¿ÉÄÜÉÐδÃ÷È·µÄ»úÖÆ,ʹµÃµÇ¸ï²¡¶¾ÒßÃçÑо¿À§ÄÑÖØÖØ,³äÂúÁËÌôÕ½¡£ÏÂÃæÖ÷Òª½éÉܽøÈëÁÙ´²ÊÔÑéµÄ¼¸ÖÖÒßÃç[9]¡£
¡¡¡¡2.2.1¡¢ ¼õ¶¾»îÒßÃç[2]
¡¡¡¡µÇ¸ïÒßÃçµÄÑо¿¿ÉÒÔ×·Ëݵ½1976Äê,WHO¶«ÄÏÑÇÇøÓòÑо¿×ÉѯίԱ»á(SEA/ACMR)µÚ1´Î»áÒéÔÚеÂÀïÕÙ¿ª,½«µÇ¸ïÈÈÑо¿ÄÉÈëÁËÓÅÏÈÊÂÏî¡£ÔÚ1976Äê8ÔµÄSEA/ACMRµÚ2´Î»áÒéÖÐ,ÔÙ´ÎÃ÷È·µÇ¸ïÈÈÑо¿µÄÖØÒªÐԺͽôÆÈÐÔ,²¢ÔÚµÚ2Äê2ÔÂÃ÷È·ÁËÒßÃçÑо¿µÄÖØÒªÐÔ¡£1978Äê,WHOÖ¸¶¨Ì©¹úMahidal´óѧ³Ðµ£ÒßÃçÑз¢ÈÎÎñ¡£1993Äê,Mahidal´óѧÓëÈüŵ·Æ°Í˹µÂÇ©ÊðºÏ×÷ÐÒé,¹²Í¬Ñз¢µÇ¸ïÈÈËļۼõ¶¾»îÒßÃç¡£ÔÚ1980-1995Äê,WHOÀúʱ15ÄêÏȺóͶÈë250ÍòÃÀÔªÍê³ÉÁË´ÓÑз¢µ½ÁÙ´²ÊÔÑéµÄһϵÁй¤×÷,È»¶ø×îÖÕÒÔʧ°Ü¸æÖÕ¡£ºóÀ´,ÃÀ¹ú¹ú·À²¿ÏÂÊôµÄÎÖ¶ûÌØÀïµÂ½¾üÑо¿Ëù(WRAIR)ºÍ¸ðÀ¼ËØÊ·¿Ë¹«Ë¾Ò²ÓÃÏàͬ¼¼ÊõÑз¢Á˼õ¶¾»îÒßÃçTDENV LAV,ÁÙ´²ÊÔÑéÖгöÏÖÃâÒßÓ¦´ð²»Æ½ºâ¡¢Ð§¼Û²»ÀíÏë,ÒÔ¼°³öÏÖ·¢ÈÈ¡¢²¡¶¾ÑªÖ¢µÈ²»Á¼·´Ó¦,×îÖÕ¸ðÀ¼ËØÊ·¿Ë¹«Ë¾Í˳ö,WRAIRÔò½«´Ë×÷Ϊ²¹Ç¿¼Á¡£
¡¡¡¡2.2.2¡¢ Ñǵ¥Î»ÒßÃç[9]
¡¡¡¡Ä¬É³¶«¹«Ë¾¿ª·¢µÄV180ÒßÃç,ÒÔ°üĤEµ°°×µÄ±£ÍâÇø×÷Ϊ¿¹Ô,Òò°ûÍâÇøÐòÁÐÕ¼Eµ°°××ÜÐòÁеÄ80%,Òò´ËÓÖ±»³ÆΪDNV-80EÒßÃç¡£Eµ°°×ÊǵǸﲡ¶¾×îÖØÒªµÄ¿¹Ìå°Ðµã,º¬·á¸»µÄÖкͿ¹Ô±íλºÍѪÇåÌØÒìÐÔ±íλ,¿ÉÓÕµ¼ÖкÍÐÔ¿¹Ìå,Òò´Ë±»¹ã·ºÓÃÓÚÑǵ¥Î»ÒßÃçÉè¼Æ¡£4ÖÖѪÇåÐ͵Ǹﲡ¶¾µÄV180µ°°×ÔÚ¹ûÓ¬S2ϸ°û±í´ï´¿»¯ºó,ÓëSSCOMATRIXTM×ô¼ÁºÍNS1µ°°×»ìºÏÐγÉV180ÒßÃç,·Ö±ðÓÚµÚ0¡¢1¡¢2¡¢3Ô¹²4´Î½ÓÖÖÎ޵Ǹﲡ¶¾¸ÐȾʷµÄ½¡¿µÈËȺ¡£¸ÃÒßÃç¿ÉÓÕµ¼²úÉúÕë¶Ô4ÖÖѪÇåÐ͵ÄÖкͿ¹ÌåºÍϸ°ûÃâÒß,µ«ÎÞÂÛÊǵ¥¼ÛÃâÒß»¹ÊÇËļÛÃâÒß,Ëù²úÉúµÄÖкÍÐÔ¿¹Ìå¾ù³öÏÖÁËÃâÒßÓ¦´ð²»¾ùºâ,¼´ÊÜÊÔÕß²úÉúµÄDV1¡¢DV2ÖкÍÐÔ¿¹Ìå×ÜÊǸßÓÚDV3¡¢DV4ÐÍ¡£¸ÃÏîÄ¿ÁÙ´²ÊÔÑé´Ó2012ÄêÕýʽÆô¶¯,2014ÄêÍê³ÉÁÙ´²¢ñÆÚÑо¿,ºóÐøδ¼û¸ÃÒßÃçµÄ½øÒ»²½Ñо¿±¨µÀ¡£½üÄêÕë¶ÔµÇ¸ï²¡¶¾²»Í¬¿¹Ôµ°°×Éè¼ÆµÄDNAÑǵ¥Î»ÒßÃçÓÐеĽøÕ¹[6]¡£°üÀ¨Õë¶ÔNS1\NS3\NS5Éè¼ÆµÄDNAÖØ×éÒßÃç¿ÉÒÔÓÕµ¼½Ï¿íÆ×ϵµÄTϸ°ûÓ¦´ð¡¢µÈ¼ÛEµ°°×¶þ¾ÛÌåÒßÃçÌÞ³ýÁËÇ°Mµ°°×ÓëEµ°°×µÄÈںϻ·,ÓÐЧ¹æ±ÜÁËADE½»²æ·´Ó¦·çÏÕ¡¢Í¨¹ýµÇ¸ï²¡¶¾ÖкͿ¹Ìå·´ÏòÑ°ÕÒÖкÍÐÔ±íλ¾ùÈ¡µÃ½ÏÀíÏëЧ¹û,ÓдýºóÆÚÁÙ´²ÊÔÑéÑéÖ¤[10,11,12,13]¡£
¡¡¡¡2.2.3¡¢ Ãð»î´¿»¯ÒßÃç[9]
¡¡¡¡ÃÀ¹ú¹ú·À²¿WRAIRºÍ¸ðÀ¼ËØÊ·¿Ë¹«Ë¾ÔÙ¶ÈÁªÊÖ,²¢ÁªºÏ°ÍÎ÷ÎÀÉú²¿ÏÂÊôµÄFiocruzºÍBio-Manguinhos¹²Í¬¿ª·¢ÁËÃð»î´¿»¯ÒßÃçTDENV PIV¡£¸ÃÒßÃçÖ÷Òª³É·ÖΪÃð»î´¿»¯µÄµÇ¸ï²¡¶¾,ÅäºÏ×ô¼Á½øÐнÓÖÖ,Ö»½ÓÖÖ2´Î,¼ä¸ô4ÖÜ¡£2012Äê,·Ö±ðÔÚÃÀ¹úºÍ²¨¶àÀè¸÷(·Ö±ð´ú±íÁ˵ǸïÈȵĵÍÁ÷ÐеØÇøºÍ¸ßÁ÷ÐеØÇø)Æô¶¯Á˸ÃÒßÃçµÄÁÙ´²ÊÔÑ顣Լƻ®ÔÚ2018Ä깫²¼ÊÔÑé½á¹û,µ«ÖÁ½ñÈÔδ¼û±¨µÀ¡£¸ÃÒßÃçÖÂÃüȱµãÊÇÃâÒßÔÐԽϵÍ,¸Ä½ø×ô¼ÁºóÔÚºï×ÓʵÑé»ñµÃ½ÏºÃЧ¹û[14]¡£
¡¡¡¡2.2.4¡¢ ǶºÏÐͼõ¶¾»îÒßÃç[15]
¡¡¡¡²ÉÓûùÒòÖØ×é¼¼Êõ,ÒÔ»ÆÈȲ¡¶¾»ùÒò×éΪ»ù±¾¹Ç¼Ü,½«PrM¡¢Eµ°°×»ùÒòÖû»³ÉµÇ¸ï²¡¶¾ÏàÓ¦µÄµ°°×»ùÒò,»ñµÃµÇ¸ï²¡¶¾Ç¶ºÏÐͼõ¶¾»îÒßÃç¡£Èüŵ·Æ°Í˹µÂ¹«Ë¾µÄCYD-TDV¡¢ÎäÌ﹫˾µÄDENVaxºÍÃÀ¹ú¹úÁ¢ÎÀÉúÑо¿Ôº¹ýÃôÓ봫Ⱦ²¡Ñо¿ËùµÄTV003¾ùÊôÓÚ¸ÃÀàÒßÃç¡£Èüŵ·Æ°Í˹µÂ¹«Ë¾µÄCYD-TDVÒßÃç(ÉÌÆ·ÃûDengvaxia)Ðè½ÓÖÖ3´Î,·Ö±ðÓÚµÚ0¡¢6¡¢12Ô½ÓÖÖ¡£¸ÃÒßÃçÁÙ´²ÊÔÑé´Ó2009ÄêÆô¶¯,2014ÄêÍê³É¢óÆÚËæ»úÊÔÑé,2015Äê12ÔÂÔÚÄ«Î÷¸ç¡¢·ÆÂɱöºÍ°ÍÎ÷ÒÀ´Î»ñÅúÉÏÊÐ,³ÉΪȫÇòÊ׸ö»ñÅúµÄµÇ¸ïÈÈÒßÃç¡£µ½Ä¿Ç°ÎªÖ¹,¸ÃÒßÃçÔÚÄ«Î÷¸ç¡¢·ÆÂɱö¡¢°ÍÎ÷¡¢É³¶ûÍ߶ࡢ¸ç˹´ïÀè¼Ó¡¢°ÍÀ¹ç¡¢Î£µØÂíÀ¡¢Ãس¡¢Ó¡Äᡢ̩¹ú¡¢Ð¼ÓƵÈ11¸ö¹ú¼Ò±»Åú×¼ÉÏÊÐ,ÔÚίÄÚÈðÀ¡¢ºé¶¼À˹¡¢ÂíÀ´Î÷ÑÇ¡¢°Ä´óÀûÑÇ¡¢°¢¸ùÍ¢¡¢ÃϼÓÀ¡¢¼íÆÒÕ¯ºÍÃÀ¹úµÈ9¸ö¹ú¼Ò»ñµÃÅú×¼[16]¡£È»¶ø,2017Äê·ÆÂɱö·¢ÉúÁËÊ®¼¸Àý¶ùͯ½ÓÖÖ¸ÃÒßÃçºó³öÏÖÖØÖ¢µÇ¸ïÈÈÉõÖÁ²»ÐÒËÀÍöµÄʼþ,¸øÒßÃçÑÐÖÆÕßµ±Í·Ò»°ô¡£·ÆÂɱöÁ¢¼´Í£Ö¹Á˸ÃÒßÃçÏúÊÛ²¢ÒªÇó°Í˹µÂ¹«Ë¾Åâ³¥[17,18]¡£ËæºóµÄÑо¿±íÃ÷,¸ÃÒßÃç½ö¶ÔÓеǸﲡ¶¾¸ÐȾʷµÄÈËȺÊÊÓÃ,¶ÔÎÞ¸ÐȾʷÈËȺÓмÓÖظÐȾºó²¡ÇéµÄ·çÏÕ[19]¡£³öÓÚ¶ÔÏû·ÑÕ߸ºÔðµÄ×ÚÖ¼,2017Äê12ÔÂÈüŵ·ÆÖ÷¶¯ÌáÒéÏà¹ØÅú×¼¹ú¼Ò²»ÔÙ¼ÌÐøʹÓøÃÒßÃç¡£2019Äê5ÔÂ,ÃÀ¹úFDAÅú×¼¸ÃÒßÃç¿ÉÒÔÓÃÓÚÓеǸﲡ¶¾¸ÐȾʷµÄ9¡«16ËêÇàÉÙÄê[20]¡£
¡¡¡¡ËäÈ»¶Ô2000-2017Ä깫¿ª·¢±íµÄÒßÃçÁÙ´²ÊÔÑéÊý¾Ý½øÐÐϵͳMeta·ÖÎö֤ʵÈüŵ·ÆÒßÃçûÓб£»¤Ð§¹û[21],¼øÓÚ½üÄêÀ´È«ÇòµÇ¸ïÒßÇéµÄÑϾþÐÔ,WHOÍƼöÔڵǸïÁ÷ÐеØÇø¶Ô¾²¡¶¾Ñ§¼ø¶¨ÓÐÃ÷È·µÇ¸ï²¡¶¾¸ÐȾʷÈËȺ¿ÉÒÔÌõ¼þÏÞÖÆÐÔ½ÓÖÖ[22]¡£¼ÈÍùµÇ¸ï²¡¶¾¸ÐȾʷֱ½ÓÓ°ÏìÈüŵ·ÆÒßÃçµÄ°²È«ÐÔºÍÓÐЧÐÔ¡£Òź¶µÄÊÇ,Ä¿Ç°ÁÙ´²ÉÐÎÞ¿É¿¿µÄ²¡¶¾Ñ§Ö¤ÊµµÇ¸ï²¡¶¾¸ÐȾµÄ¿ìËÙÕï¶Ï¼ì²â·½·¨[23]¡£
¡¡¡¡ÃÀ¹ú¹ýÃôÓ봫Ⱦ²¡Ñо¿ËùµÄTV003ÒßÃçÓÚ2011ÄêÆô¶¯ÁÙ´²ÊÔÑé,Ä¿Ç°ÔÚ°ÍÎ÷½øÐдó¹æÄ£ÁÙ´²ÊÔÑé,ÔÚÌ©¹úºÍÃϼÓÀ¹ú½øÐТòÆÚÊÔÑé¡£½üÆÚÁÙ´²ÊÔÑé½á¹ûÏÔʾÁ¼ºÃÃâÒßÔÐԺͰ²È«ÐÔ[9,24]¡£ÈÕ±¾ÎäÌ﹫˾µÄDENVax(TDV,TAK-003)ÒßÃçÓÚ2010ÄêÕýʽÆô¶¯ÁÙ´²ÊÔÑé,2017Äê11Ô¹«²¼µÄ¢òÆÚ½á¹ûÏÔʾ2¡«17ËêÇàÉÙÄê¶ùͯ½ÓÖÖºóÓ¦´ðЧ¹û³ÖÐø18¸öÔÂ,ÔÚ2018ÄêÍê³ÉÁÙ´²¢óÆÚÊÔÑé,ÁÙ´²ÊÔÑé½á¹ûÏÔʾ¸ÃÒßÃç¾ßÓÐÁ¼ºÃÃâÒßÔÐԺͰ²È«ÐÔ[25,26]¡£
¡¡¡¡3¡¢ µÇ¸ï²¡¶¾Ã½½é¿ØÖÆ
¡¡¡¡µÇ¸ïÈÈÖ÷Òª¾ÓÉÒÁÎö£Ò§¶ø´«²¥,Òò´ËÑо¿ÎÃýµÄ·À¿Ø¶ÔÓÚ´ËÀ༲²¡µÄ·ÀÖηdz£ÖØÒª¡£ÓÉÓÚ´«Í³µÄ»¯Ñ§Ò©Îï·½·¨¶Ô¸ÃÀàÎÃý¿ØÖÆЧ¹û²»¼Ñ,³£Óû¯Ñ§É±³æ¼ÁDDT³¤ÆÚʹÓÃÈÝÒײúÉúÄÍÒ©,ÇÒ¶Ô»·¾³ÓÐÎÛȾΣº¦,Òò´Ë²ÉÓÃÉúÎïÎÃý·À¿ØµÄ²ßÂÔÓ¦Ô˶øÉú[27]¡£
¡¡¡¡´«Í³µÄÉúÎï·À¿Ø²ßÂÔÀûÓÃ΢ÉúÎïɱ³æ,ÈçËÕÔƽðÑ¿æ߸˾úBT»òÕæ¾úɱ³æÒòЧÂʵÍÏÞÖÆÁËÓ¦Óá£ÔÚ¹ýÈ¥20ÄêÀï,¸÷ÖÖ´´ÐÂÐÔµÄÎóæ¿ØÖƲßÂÔ±»Ñз¢³öÀ´,ÒÔ¼õÉÙЯ´øÖ²¡²¡¶¾ºÍϸ¾úµÄÎó洫²¥¡£ÕâЩ²ßÂÔ°üÀ¨¼õÉÙÎóæÖÖȺÊýÁ¿(³ÆΪÖÖȺÒÖÖÆ)»òͨ¹ý×ÔÈ»ÖÖȺ´«²¥»ùÒòÐÞÊλòϸ¾ú¸ÐȾʹҰÉúÎóæÎÞ·¨´«²¥´«È¾²¡(³ÆΪÖÖȺÖû»)[27,28]¡£ÀýÈç,Éú»îÔÚÀ¥³æ¼ÄÖ÷ϸ°ûÖеÄĸϵÒÅ´«µÄÎÖ¶û°Í¿Ë¾úÊôµÄϸ¾úÉú»îÔÚÀ¥³æ¼ÄÖ÷µÄϸ°ûÖÐ,ËüÃÇÊÇĸϵÒÅ´«µÄ,ÊÇÒ»ÖÖ¼ÈÄÜÒÖÖÆÖÖȺÓÖÄܽøÐÐÖÖȺÖû»µÄ·½Ê½Ó°ÏìËÞÖ÷µÄ·±Ö³¡£¼´,µ±¸ÐȾijÖÖÎÖ¶û°Í¿Ë¾úµÄÐÛÐÔÎÃ×Ó±»ÊͷŲ¢Óëδ¸ÐȾͬһÖÖÎÖ¶û°Í¿Ë¾úµÄÒ°Éú´ÆÐÔÎÃ×Ó½»Åäʱ,´ÆÐÔÎÃ×Ó¾ÍÎÞ·¨²úÉú»îÂÑ¡£»òÕß,µ±ÊÍ·ÅËùÓдóÁ¿¸ÐȾÎÖ¶û°Í¿Ë¾úµÄÐÛÐԺʹÆÐÔÎÃ×Óʱ,½«Ê¹ÎÃ×Ó´«²¥²¡¶¾µÄÄÜÁ¦½µµÍ,¿ÉÄܵ¼ÖÂÕâÖÖ¾úÖêÔÚÒ°ÉúÖÖȺÖд«²¥,´Ó¶øʹÎÃ×Ó´«²¥²¡¶¾µÄÄÜÁ¦½µµÍ¡£Ä¿Ç°,À¥³æ²»Óý¼¼Êõ(sterile insect technique,SIT)Òѱ»³É¹¦ÔËÓÃÓÚÅ©ÒµÉú²ú,ÓÐЧ¿ØÖÆÁ˶àÖÖÖØҪũҵº¦³æµÄÊýÁ¿¡£¸Ã¼¼Êõͨ¹ýÊͷž·øÉäµ¼ÖµľøÓýÐÛ³æÓëÒ°Éú´Æ³æ½»Åä,ʹÆäÎÞ·¨²úÉú×Ó´ú,´ïµ½½µµÍº¦³æÖÖȺÊýÁ¿µÄÄ¿µÄ¡£SIT¿ØÖÆÎóæµÄÇ°¾°ÉÐÔÚ̽Ë÷ÖÐ,Ä¿Ç°¸Ã¼¼Êõ´æÔÚµÄÒ»¸öȱµãÊÇ·øÉä»á½µµÍÐÛÎý»ÅäµÄ¾ºÕùÁ¦ºÍÉú´æÁ¦¡£
¡¡¡¡À¥³æ²»ÏàÈݼ¼Êõ(incompatible insect technique,IIT)ÓÐÍû¿Ë·þSIT¼¼ÊõµÄijЩ²»×ã¡£¸Ã¼¼ÊõÖ÷Ҫͨ¹ýÊÍ·ÅЯ´øÓÐÓëÒ°ÉúÐÛÎò»Í¬ÖÖÎÖ¶û°Í¿Ë¾ú(wolbachia)µÄÐÛÎÃ,ÓÕ·¢°ûÖʲ»ÈÝʹ´ÆÎò»Óý¡£Àú¾50ÄêÏà¹Ø̽Ë÷Ñо¿Ö¤Ã÷,SIT¡¢IITÁªºÏʹÓÿÉÒÔ»ñµÃÀíÏëЧ¹û,ÓÈÆäÔÚ½ü2Äê»ñµÃÁËÍ»ÆÆÐÔ½øÕ¹[29]¡£2016Äê,°Ä´óÀûÑÇO’NEILLµÈ[30]Ê״ᨵÀÁËС¹æÄ£ÏÖ³¡ÊÔÑéÊÍ·ÅÈ˹¤×ªÈ¾WolbachiaµÄÎóæ½øÐÐÖÖȺѹÖÆ¡£2019Äê7ÔÂ18ÈÕÖйúÞÉÖ¾ÓÂÍŶÓͨ¹ýÏÖ³¡ÊÔÑé֤ʵIIT-SITÏà½áºÏ¿ÉÒÔ¶ÔÎÃýÖÖȺ½øÐÐÇøÓòÐÔ¿ØÖÆ[31]¡£¸ÃÍŶÓͨ¹ýÅßÌ¥ÏÔ΢עÉä¼¼Êõ,½«¿âÎÃÌåÄÚµÄWalbachia wPipתÒƵ½°×ÎÆÒÁÎÃHCÎÃÖêÌåÄÚ,ͬʱ, ¶ÔHC´ÆÎýøÐеͼÁÁ¿·øÉäºó,°´2%±ÈÀý½«ÆäÊÍ·Å»ìÈëÒ°ÉúÖÖȺÖС£¾¹ý2¡«3Äê³ÖÐøÊÍ·Å,ÔÚ2¸öÊÔÑéÏÖ³¡»ù±¾Çå³ý»ò½Ó½üÇå³ýÁË°×ÎÆÒÁÎõÄÖÖȺÊýÁ¿,2ÄêÄÚÒ°Éú³ÉÎÃÊýÁ¿Æ½¾ù¼õÉÙÁË83%¡«94%,³ÖÐø6ÖÜÄÚ¼ì²â²»µ½ÈκγÉÎá£Ò°ÉúÓ׳æÊýÁ¿Äê¶Èƽ¾ù¼õÉÙ³¬¹ý94%,³ÖÐø13ÖÜδ¼ì²âµ½´æ»îÎÃÂÑ¡£¸ÃÑо¿½á¹û±»WHOºÍ¹ú¼ÊÔ×ÓÄÜ»ú¹¹µÈÁªºÏ¹ú»ú¹¹ÈϿɲ¢ÏòÈ«ÇòÍƼö¡£
¡¡¡¡4¡¢ Õ¹Íû
¡¡¡¡ÎãÓ¹ÖÃÒÉ,·¢Õ¹ºÍ¸Ä½ø°²È«ÓÐЧµÄµÇ¸ïÒßÃçÊÇÓ¦µ±ÓÅÏÈ¿¼ÂǵÄÎÊÌâ[9]¡£ËäÈ»Èüŵ·Æ°Í˹µÂ¹«Ë¾µÄÒßÃçÑÐÖÆʧ°Ü,µ«ÆäÁÙ´²ÊÔÑé½á¹ûºÍʧ°Ü¾Ñé¸øÁËÎÒÃǸü¶àÆôʾ,¶Ô½ñºóµÇ¸ïÒßÃçÑз¢ÓкܺõĽè¼øÒâÒå¡£±ÈÈçÁÙ´²ÊÔÑéÒѾÃ÷È·½¨Á¢µÄÊÉ°ßÒÖÖÆÖкÍʵÑé(PRNT)ÊǽñºóÆÀ¼ÛÒßÃçÖкÍÐÔ¿¹ÌåµÄ½ð±ê×¼[32];Ò»¸öÀíÏëµÄµÇ¸ïÈȱ£»¤ÐÔÒßÃçÓ¦¸Ãͬʱ¾ß±¸ÊʶȵÄÌìÈ»ÃâÒßÓ¦´ð,°üÀ¨ÖеÈÇ¿¶ÈµÄÑ×ÐÔÒò×Ó(IL-6,IL-8,TNF-α, IFN-α/β)ÒÔ¼°Á¬½ÓÌìÈ»ÃâÒߺͻñµÃÐÔÃâÒßµÄÇ÷»¯Òò×Ó,Bϸ°ûÓ¦´ðˮƽ²úÉú¸ßЧ¼Û¡¢ÌØÒìÐÔ¡¢½»²æ·´Ó¦ÐÔµÄÖкÍÐÔ¿¹Ìå[33],Tϸ°ûˮƽӦ´ð²úÉú½á¹¹µ°°×ºÍ/»ò·Ç½á¹¹µ°°×ÌØÒìÐÔµÄTh1/CTL,·ÖÃÚ¿É¿ØÐÔÑ×ÐÔ¹¦ÄÜÒò×Ó,IFN-γŨ¶È¸ßÓÚTNF-α¡£Ï¸°ûÒò×ÓÊÍ·ÅˮƽºÍÏà¹Ø¶¯Á¦Ñ§Æ×Ö±½ÓÓ°ÏìÒßÃç±£»¤ÐÔ½á¾Ö[34]¡£ËäÈ»µÇ¸ïÒßÃç½øÕ¹À§ÄÑÖØÖØ,µ«ÊÀ½ç¸÷¹úÈÔÈ»ÔÚÇ°Æͺó¼ÌµØ½øÐÐÏà¹ØÑо¿,ÒÔÆÚ¹¥¿ËÕâ¸öÄÑÌâ¡£Ïà¹ØºòÑ¡ÒßÃçÁÙ´²ÊÔÑé½á¹ûÒ²ÁîÈËÆÚ´ý¡£ÎÒ¹úÇ廪´óѧ³Ì¹¦ÍŶÓ,¾ü¿ÆÔºÇسɷ塢ÇضõµÂÍŶÓ,Ê׶¼Ò½¿Æ´óѧ°²¾²ÍŶÓ,ÖпÆÔº½ðÏÀÍŶÓ,½¾ü¾üÒ½´óѧÈÄÏͲÅÍŶӺÍÀî½úÌÎÍŶӵȾùÖÂÁ¦ÓڵǸïÒßÃçÑо¿,Ò²»ñµÃ²»ÉÙÁîÈ˹ÄÎèµÄÇ°ÆÚʵÑé½á¹ûºÍÁîÈËÆÚ´ýµÄÓ¦ÓÃÇ°¾°[35,36,37,38,39,40]¡£
¡¡¡¡´ËÍâ,ÉúÎï¼¼ÊõµÄ¿ìËÙ·¢Õ¹¸øý½é·À¿Ø´øÀ´ÎÞÏÞ¿ÉÄÜ,δÀ´ÎÃý¿ØÖÆ¿ÉÄÜÔÚÒÔϼ¸¸ö·½ÃæÈ¡µÃÍ»ÆÆ[41,42]:À¥³æºÏ³ÉÉúÎïѧÑо¿,ÕûºÏºÏ³É»ùÒòºÍ±ê¼ÇÐÔ×´,½µµÍ´«È¾ÄÜÁ¦,¿ØÖÆ»òÇå³ýijÀàÓк¦ÖÖȺ;»ùÓÚºËËáøϵͳCRISPR-cas9È˹¤¹¹½¨×Ô˽DNAϵͳ,Æä¾ßÓм«Ç¿×ÔÎÒ·±Ö³ÄÜÁ¦,¿ÉÒÔÔÚij¸öÖÖȺ»ò¶àÖÖȺ¼ä·è¿ñ´«²¥[43];»ùÒò¹¤³Ì±à¼¼¼Êõ½¨Á¢ÏÔÐÔ²»×ã»ùÒòÇý¶¯ÏµÍ³,¾«×¼°ÐÏòij¸öº¦³æÖÖȺ,¶ø²»ÊÇÕûÀàÖÖȺ½øÐпØÖÆ[27]¡£
¡¡¡¡µÇ¸ïÈÈÔÚÈ«ÇòÒѳÉΪһ¸öÑÏÖصĹ«¹²ÎÀÉúÎÊÌ⡣ȫÇò±äůʹԱ¾½öËÁÅ°ÓÚÈÈ´øºÍÑÇÈÈ´øµØÇøµÄµÇ¸ïÈÈÖ𽥿ªÊ¼ÏòδøºÍº®´øµØÇøºÍ¹ú¼ÒÀ©É¢¡£¾Ý±¨µÀ,ÒÁÎÃÀúÀ´Ö»Éú»îÔÚº£°Î1 000 mÒÔϵØÇø,µ«Ëæ×ÅÆøºò±äů,µ¼ÖÂÄÏÃÀº£°Î1 350¡«-2 200 m¸ßµÄµØÇø¾¹ÒÑÒ²·¢ÏÖ¿ªÊ¼ÓÐÒÁÎóöû¡£Í¬Ê±,Óú·¢Æµ·±µÄ¹ú¼Ê½»Á÷ºÍ¾¼ÃóÒס¢ÂÃÓεķ¢Õ¹½«¼Ó¾çµÇ¸ïÈÈÔÚÊÀ½ç·¶Î§ÄÚµÄÂûÑÓ¡£¿ÉÒÔÔ¤¼û,21ÊÀ¼ÍµÇ¸ïÈÈÁ÷ÐгÊÉÏÉýÇ÷ÊÆ,δÀ´·À¿ØÈÎÎñ½«¸ü¼ÓÑϾþ¡£·ÀÖØÓÚÖÎ,µÇ¸ïÒßÃçµÄÑо¿ºÍÎóæ·ÀÖν«ÊÇδÀ´µÇ¸ïÈÈ·À¿ØÑо¿µÄÖ÷ÐýÂÉ¡£
¡¡¡¡²Î¿¼ÎÄÏ×
¡¡¡¡[1] World Healthy Organization.Dengue control[EB/OL].https://www.who.int/denguecontrol/disease/en/.
¡¡¡¡[2] MARIMUTHU P,RAVINDER J R.Trends in clinical trials of dengue vaccine[J].Perspect Clin Res,2016,7(4):161-164.DOI:10.4103/2229-3485.192035.http://outbreaks.globalincidentmap.com/.
¡¡¡¡[3] TORRESI J,EBERT G,PELLEGRINI M.Vaccines licensed and in clinical trials for the prevention of dengue[J].Hum Vaccin Immunother,2017,13(5):1059-1072.DOI:10.1080/21645515.2016.1261770.
¡¡¡¡[4] Dutbreaks:Displaying outbreaks,case and deaths from viral and bacterial diseases which have the potential to indicate biological terrorism[EB/OL].http://outbreaks.globalincidentmap.com/.
¡¡¡¡[5] MART?NEZ-VEGA R A,CARRASQUILA G,LUNA E,et al.ADE and dengue vaccination[J].Vaccine,2017,35(32):3910-3912.DOI:10.1016/j.vaccine.2017.06.004.
¡¡¡¡[6] SLON-CAMPOS J L,DEJNIRATTISAI W,JAGGER B W,et al.A protective Zika virus E-dimer-based subunit vaccine engineered to abrogate antibody-dependent enhancement of dengue infection[J].Nat Immunol.2019.[Epub ahead of print].DOI:10.1038/s41590-019-0477-z.
¡¡¡¡[7] DORIGATTI I,DONNELLY C A,LAYDON D J,et al.Refined efficacy estimates of the Sanofi Pasteur dengue vaccine CYD-TDV using machine learning[J].Nat Commun,2018,9(1):3644.DOI:10.1038/s41467-018-06006-6.
¡¡¡¡[8] PAESSLER S,WALKER D H.Pathogenesis of the viral hemorrhagic fevers[J].Annu Rev Pathol,2013,8:411-440.DOI:10.1146/annurev-pathol-020712-164041.
¡¡¡¡[9] PROMPETCHARA E,KETLOY C,THOMAS S J,et al.Dengue vaccine:global development update[J].Asian Pac J Allergy Immunol,2019.[Epub ahead of print].DOI:10.12932/AP-100518-0309.
¡¡¡¡[10] KAO Y S,YU C Y,HUANG H J,et al.Combination of modified NS1 and NS3 as a novel vaccine strategy against dengue virus infection[J].J Immunol,2019.[Epub ahead of print].DOI:10.4049/jimmunol.1900136.
¡¡¡¡[11] LI L K,MENG W X,HORTON M,et al.Potent neutralizing antibodies elicited by dengue vaccine in rhesus macaque target diverse epitopes[J].PLoS Pathog,2019,15(6):e1007716.DOI:10.1371/journal.ppat.1007716.
¡¡¡¡[12] ROTH C,CANTAERT T,COLAS C,et al.A modified mRNA vaccine targeting immunodominant NS epitopes protects against dengue virus infection in HLA class I transgenic mice[J].Front Immunol,2019,10:1424.DOI:10.3389/fimmu.2019.01424.
¡¡¡¡[13] WANG R,GAO N,LI Y,et al.Cross-protection against four serotypes of dengue virus in mice conferred by a zika DNA vaccine[J].Front Cell Infect Microbiol,2019,9:147.DOI:10.3389/fcimb.2019.00147.
¡¡¡¡[14] FERNANDEZ S,THOMAS S J,DE LA BARRERA R,et al.An adjuvanted,tetravalent dengue virus purified inactivated vaccine candidate induces long-lasting and protective antibody responses against dengue challenge in rhesus macaques[J].Am J Trop Med Hyg,2015,92(4):698-708.DOI:10.4269/ajtmh.14-0268.
¡¡¡¡[15] WILDER-SMITH A,HOMBACH J,FERGUSON N,et al.Deliberations of the strategic advisory group of experts on immunization on the use of CYD-TDV dengue vaccine[J].Lancet Infect Dis,2019,19(1):e31-e38.DOI:10.1016/S1473-3099(18)30494-8.
¡¡¡¡[16] TORRESI J,EBERT G,PELLEGRINI M.Vaccines licensed and in clinical trials for the prevention of dengue[J].Hum Vaccin Immunother,2017,13(5):1059-1072.DOI:10.1080/21645515.2016.1261770.
¡¡¡¡[17] DYER O.Philippines to charge Sanofi staff and government officials over dengue vaccine[J].BMJ,2019,364:l1088.DOI:10.1136/bmj.l1088.
¡¡¡¡[18] COHEN J.Controversy over dengue vaccine risk[J].Science,2019,365(6457):961-962.DOI:10.1126/science.365.6457.961.
¡¡¡¡[19] SRIDHAR S,LUEDTKE A,LANGEVIN E,et al.Effect of dengue serostatus on dengue vaccine safety and efficacy[J].N Engl J Med,2018,379(4):327-340.DOI:10.1056/NEJMoa1800820.
¡¡¡¡[20] VOELKER R.Dengue vaccine gets the nod[J].JAMA,2019,321(21):2066.DOI:10.1001/jama.2019.6886.
¡¡¡¡[21] DA SILVEIRA L T C,TURA B,SANTOS M.Systematic review of dengue vaccine efficacy[J].BMC Infect Dis,2019,19(1):750.DOI:10.1186/s12879-019-4369-5.
¡¡¡¡[22] TORRES J R,FALLEIROS-ARLANT L H,GESSNER B D,et al.Updated recommendations of the international dengue initiative expert group for CYD-TDV vaccine implementation in Latin America[J].Vaccine,2019.[Epub ahead of print].DOI:10.1016/j.vaccine.2019.09.010.
¡¡¡¡[23] LUO R,FONGWEN N,KELLY-CIRINO C,et al.Rapid diagnostic tests for determining dengue serostatus:a systematic review and key informant interviews[J].Clin Microbiol Infect,2019,25(6):659-666.DOI:10.1016/j.cmi.2019.01.002.
¡¡¡¡[24] POPPER S J,STROUTS F R,LINDOW J C,et al.Early transcriptional responses after dengue vaccination mirror the response to natural infection and predict neutralizing antibody titers[J].J Infect Dis,2018,218(12):1911-1921.DOI:10.1093/infdis/jiy434.
¡¡¡¡[25] WHITEHEAD S S.Development of TV003/TV005,a single dose,highly immunogenic live attenuated dengue vaccine;what makes this vaccine different from the Sanofi-Pasteur CYDTM vaccine?[J].Expert Rev Vaccines,2016;15(4):509-517.DOI:10.1586/14760584.2016.1115727.
¡¡¡¡[26] S?EZ-LLORENS X,TRICOU V,YU D L,et al.Immunogenicity and safety of one versus two doses of tetravalent dengue vaccine in healthy children aged 2-17 years in Asia and Latin America:18-month interim data from a phase 2,randomised,placebo-controlled study[J].Lancet Infect Dis,2018 ,18(2):162-170.DOI:10.1016/S1473-3099(17)30632-1.
¡¡¡¡[27] SHAW W R,CATTERUCCIA F.Vector biology meets disease control:using basic research to fight vector-borne diseases[J].Nat Microbiol,2019,4(1):20-34.DOI:10.1038/s41564-018-0214-7.
¡¡¡¡[28] ARMBRUSTER P A.Tiger mosquitoes tackled in a trial[J].Nature,2019,572(7767):39-40.DOI:10.1038/d41586-019-02000-0.
¡¡¡¡[29] O’NEILL S L,RYAN P A,TURLEY A P,et al.Scaled deployment of Wolbachia to protect the community from dengue and other Aedes transmitted arboviruses[J].Gates Open Res,2018,2:36.DOI:10.12688/gatesopenres.12844.2.
¡¡¡¡[30] O’NEILL S L.Wolbachia mosquito control:tested[J].Science,2016,352(6285):526.DOI:10.1126/science.352.6285.526-a.
¡¡¡¡[31] ZHENG X Y,ZHANG D J,LI Y J,et al.Incompatible and sterile insect techniques combined eliminate mosquitoes[J].Nature,2019,572(7767):56-61.DOI:10.1038/s41586-019-1407-9.
¡¡¡¡[32] SCREATON G,MONGKOLSAPAYA J.Which dengue vaccine approach is the most promising,and should we be concerned about enhanced disease after vaccination?the challenges of a dengue vaccine[J].Cold Spring Harb Perspect Biol,2018,10(6):a029520.DOI:10.1101/cshperspect.a029520.
¡¡¡¡[33] POPPER S J,STROUTS F R,LINDOW J C,et al.Early transcriptional responses after dengue vaccination mirror the response to natural infection and predict neutralizing antibody titers[J].J Infect Dis,2018,218(12):1911-1921.DOI:10.1093/infdis/jiy434.
¡¡¡¡[34] ANDERSON K B,ENDY T P,THOMAS S J.The dynamic role of dengue cross-reactive immunity:changing the approach to defining vaccine safety and efficacy[J].Lancet Infect Dis,2018,18(10):e333-e338.DOI:10.1016/S1473-3099(18)30126-9.
¡¡¡¡[35] LIU Y,LIU J Y,CHENG G.Vaccines and immunization strategies for dengue prevention[J].Emerg Microbes Infect,2016,5(7):e77.DOI:10.1038/emi.2016.74.
¡¡¡¡[36] LIU Y,ZHANG F C,LIU J Y,et al.Transmission-blocking antibodies against mosquito C-type lectins for dengue prevention[J].PLoS Pathog,2014,10(2):e1003931.DOI:10.1371/journal.ppat.1003931.
¡¡¡¡[37] SUN J,LI M,WANG Y N,et al.Elaboration of tetravalent antibody responses against dengue viruses using a subunit vaccine comprised of a single consensus dengue envelope sequence[J].Vaccine,2017,35(46):6308-6320.DOI:10.1016/j.vaccine.2017.09.063.
¡¡¡¡[38] WANG R,GAO N,LI Y,et al.Cross-protection against four serotypes of dengue virus in mice conferred by a zika DNA vaccine[J].Front Cell Infect Microbiol,2019,9:147.DOI:10.3389/fcimb.2019.00147.
¡¡¡¡[39] YANG J,ZHANG J L,CHEN W,et al.Eliciting cross-neutralizing antibodies in mice challenged with a dengue virus envelope domain III expressed in Escherichia coli[J].Can J Microbiol,2012,58(4):369-380.DOI:10.1139/w11-137.
¡¡¡¡[40] YUAN J Z,YANG J,HU Z,et al.Safe staphylococcal platform for the development of multivalent nanoscale vesicles against viral infections[J].Nano Lett,2018,18(2):725-733.DOI:10.1021/acs.nanolett.7b03893.
¡¡¡¡[41] PIXLEY K V,FALCK-ZEPEDA J B,GILLER K E,et al.Genome editing,gene drives,and synthetic biology:will they contribute to disease-resistant crops,and who will benefit?[J].Annu Rev Phytopathol,2019,57:165-188.DOI:10.1146/annurev-phyto-080417-045954.
¡¡¡¡[42] LIU T,YANG W Q,XIE Y G,et al.Construction of an efficient genomic editing system with CRISPR/Cas9 in the vector mosquito Aedes albopictus[J].Insect Sci,2019,26(6):1045-1054.DOI:10.1111/1744-7917.12645.
¡¡¡¡[43] SHAPIRO R S,CHAVEZ A,PORTER C B M,et al.A CRISPR-Cas9-based gene drive platform for genetic interaction analysis in Candida albicans[J].Nat Microbiol,2018,3(1):73-82.DOI:10.1038/s41564-017-0043-0.
Õã½Äþº£µÇ¸ïÈÈÒßÇéÍø¸ñ»¯¹ÜÀíµÄ·½°¸¼°Ð§¹û
µÇ¸ïÈÈý½é°×ÎÆÒÁÎÃÔÚÄþº£Ïع㷺´æÔÚÇÒÃܶȽϸߣ¬ÎÃÓ×ÃܶÈÔ¶Ô¶³¬¹ý¿ØÖƵǸïÈÈ´«²¥ãÐÖµ£¬ÓÐÇøÓòÁ÷ÐзçÏÕ£¨BI¡Ý20£©£¬·À¿ØÎÃýæÜÉúÓ붣ҧÊÇÄ¿Ç°ÉõÖÁδÀ´½Ï³¤Ê±¼äÄÚ¿ØÖÆÒßÇéµÄΨһÓÐЧ·½·¨¡£...
¹ãÎ÷µÇ¸ïÈÈÒßÇé·À¿ØµÄÇé¿öÓë¶Ô²ß
½üÄêÀ´ÎÃý´«È¾²¡Æµ·¢,ÔÚÎÒ¹úÿÄ괫Ⱦ²¡×Ü·¢²¡²¡ÀýÖÐÕ¼5%¡«10%,Æ䲡ËÀÊýÕ¼´«È¾²¡×ܲ¡ËÀÊýµÄ30%¡«40%¡£¹ãÎ÷µØ´¦Î÷ÄϱßÚï,ÊôÑÇÈÈ´øÓêÁÖÆøºò,Ñô¹â³ä×ã,ÓêÁ¿³äÅæ,Êʺϰ×ÎÆÒÁÎÃæÜÉú·±Ö³¡£...
Á÷ʽϸ°ûÊõÕï¶ÏµÇ¸ïÈÈ»¼ÕßTÁÜ°Íϸ°ûÃâÒßÒì³£
µÇ¸ïÈÈÊÇÓɵǸﲡ¶¾ÒýÆ𣬾ÒÁÎô«²¥µÄÒ»ÖÖ¼±ÐÔ´«È¾²¡£¬Ç±·üÆÚͨ³£Ô¼5~7d,¾ßÓд«²¥Ñ¸ÃÍ¡¢·¢²¡ÂʸߵÈÌص㡣µÇ¸ïÈÈ»¼ÕßÓпÉÄܳöÏÖ¼«¶ÈÆ£¾ë¼°ÒÖÓôÖ¢×´£¬ÉÙÊý»¼Õß»á¶ñ»¯ÖÁµÇ¸ï³öѪÈÈ£¬²¢½øÒ»²½·¢Éú³öѪ¡¢ÐÝ¿Ë£¬ÄËÖÁËÀÍö£¬µÇ¸ïÈÈÒýÆðµÄ²¢·¢Ö¢ÍùÍùÊÇ»¼ÕßÖÂËÀµÄÖ÷Òò...