Johnson Barbara W, Chambers Trudy V, Crabtree Mary B, Bhatt Tejal R, Guirakhoo Farshad, Monath Thomas P, Miller Barry R
Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado 80522, USA.
Am J Trop Med Hyg. 2002 Sep;67(3):260-5. doi: 10.4269/ajtmh.2002.67.260.
The chimeric yellow fever (YF) 17D-dengue type 2 (ChimeriVax-DEN2) vaccine virus developed by Acambis, Inc. (Cambridge, MA) contains the prM and E genes of wild-type (wt) dengue 2 (DEN-2) (strain PUO-218) virus in the YF vaccine virus (strain 17D) backbone. The potential of ChimeriVax-DEN2 virus to infect and be transmitted by Aedes aegypti, the principal DEN and YF virus mosquito vector, and Aedes albopictus, a species that occurs in areas of active transmission of YF and DEN viruses, was evaluated. Mosquitoes were intrathoracically (IT) inoculated with virus or were fed a virus-laden blood meal, and the replication kinetics of ChimeriVax-DEN2 were compared with the wt DEN-2 and YF 17D vaccine viruses. Replication of YF 17D virus is attenuated in cultured Ae. albopictus C6/36 mosquito cells and in Ae. aegypti and Ae. albopictus mosquitoes. Growth of ChimeriVax-DEN2 virus similarly was restricted in C6/36 cells and in mosquitoes. ChimeriVax-DEN2 replicated in 56% of IT inoculated Ae. aegypti, and virus disseminated to head tissue in 36%, with a mean viral titer of 1.8 log10 PFU/mosquito. Of mosquitoes, 16% of Ae. aegypti and 24% of Ae. albopictus were infected 14 days after a blood meal containing ChimeriVax-DEN2, but virus did not disseminate to head tissue. In contrast, DEN-2 replicated in all IT inoculated and orally infected Ae. aegypti (mean titer 5.5 log10 PFU/mosquito), and virus disseminated to head tissue in 95%. Of Ae. albopictus, 84% were infected after a blood meal containing DEN-2 virus; dissemination occurred in 36%. Replication of ChimeriVax-DEN2 virus in mosquitoes corresponded to that of YF 17D vaccine virus, which is restricted in its ability to infect and replicate in mosquitoes. Therefore, transmission of ChimeriVax-DEN2 virus by vector mosquitoes is unlikely.
由Acambis公司（马萨诸塞州剑桥）研发的嵌合型黄热病（YF）17D - 2型登革热（ChimeriVax - DEN2）疫苗病毒，在YF疫苗病毒（17D株）主干中包含野生型（wt）登革热2型（DEN - 2）（PUO - 218株）病毒的prM和E基因。评估了ChimeriVax - DEN2病毒感染埃及伊蚊（主要的登革热和黄热病病毒蚊媒）和白纹伊蚊（在黄热病和登革热病毒活跃传播地区出现的一种蚊子）并由其传播的可能性。用病毒对蚊子进行胸腔内（IT）接种或喂以含病毒的血餐，并将ChimeriVax - DEN2的复制动力学与野生型DEN - 2和YF 17D疫苗病毒进行比较。YF 17D病毒在培养的白纹伊蚊C6/36蚊细胞以及埃及伊蚊和白纹伊蚊中复制减弱。ChimeriVax - DEN2病毒在C6/36细胞和蚊子中的生长同样受到限制。ChimeriVax - DEN2在56%的IT接种埃及伊蚊中复制，病毒传播到头部组织的比例为36%，平均病毒滴度为1.8 log10 PFU/蚊子。在喂以含ChimeriVax - DEN2血餐14天后，16%的埃及伊蚊和24%的白纹伊蚊被感染，但病毒未传播到头部组织。相比之下，DEN - 2在所有IT接种和经口感染的埃及伊蚊中复制（平均滴度5.5 log10 PFU/蚊子），病毒传播到头部组织的比例为95%。在喂以含DEN - 2病毒血餐之后，84%的白纹伊蚊被感染；传播发生率为36%。ChimeriVax - DEN2病毒在蚊子中的复制情况与YF 17D疫苗病毒相似，其在蚊子中感染和复制的能力受限。因此，媒介蚊子传播ChimeriVax - DEN2病毒的可能性不大。
