Cabral-Miranda Gustavo, Lim Stephanie M, Mohsen Mona O, Pobelov Ilya V, Roesti Elisa S, Heath Matthew D, Skinner Murray A, Kramer Matthias F, Martina Byron E E, Bachmann Martin F
The Jenner Institute, Nuffield Department of Medicine, Centre for Cellular and Molecular Physiology (CCMP), University of Oxford, Oxford OX1 2JD, UK.
Immunology, RIA, Inselspital, University of Bern, 3010 Bern, Switzerland.
Vaccines (Basel). 2019 Jul 23;7(3):72. doi: 10.3390/vaccines7030072.
(ZIKV) is a similar to (DENV) in terms of transmission and clinical manifestations, and usually both viruses are found to co-circulate. ZIKV is usually transmitted by mosquitoes bites, but may also be transmitted by blood transfusion, via the maternal-foetal route, and sexually. After 2015, when the most extensive outbreak of ZIKV had occurred in Brazil and subsequently spread throughout the rest of South America, it became evident that ZIKV infection during the first trimester of pregnancy was associated with microcephaly and other neurological complications in newborns. As a result, the development of a vaccine against ZIKV became an urgent goal. A major issue with DENV vaccines, and therefore likely also with ZIKV vaccines, is the induction of antibodies that fail to neutralize the virus properly and cause antibody-dependent enhancement (ADE) of the infection instead. It has previously been shown that antibodies against the third domain of the envelope protein (EDIII) induces optimally neutralizing antibodies with no evidence for ADE for other viral strains. Therefore, we generated a ZIKV vaccine based on the EDIII domain displayed on the immunologically optimized (CuMVtt) derived virus-like particles (VLPs) formulated in dioleoyl phosphatidylserine (DOPS) as adjuvant. The vaccine induced high levels of specific IgG after a single injection. The antibodies were able to neutralise ZIKV without enhancing infection by DENV in vitro. Thus, the here described vaccine based on EDIII displayed on VLPs was able to stimulate production of antibodies specifically neutralizing ZIKV without potentially enhancing disease caused by DENV.
寨卡病毒（ZIKV）在传播和临床表现方面与登革病毒（DENV）相似，并且通常发现这两种病毒同时传播。寨卡病毒通常通过蚊虫叮咬传播，但也可能通过输血、母婴途径和性传播。2015年后，寨卡病毒在巴西发生了最广泛的疫情，随后蔓延到南美洲其他地区，此时很明显，妊娠头三个月感染寨卡病毒与新生儿小头畸形和其他神经并发症有关。因此，开发一种针对寨卡病毒的疫苗成为一个紧迫目标。登革病毒疫苗的一个主要问题，因此寨卡病毒疫苗可能也存在这个问题，就是诱导产生的抗体不能正确中和病毒，反而会导致感染的抗体依赖性增强（ADE）。此前已经表明，针对包膜蛋白第三结构域（EDIII）的抗体能诱导产生最佳的中和抗体，且没有证据表明对其他病毒株存在ADE。因此，我们基于展示在免疫优化的芜菁黄花叶病毒（CuMVtt）衍生的病毒样颗粒（VLP）上的EDIII结构域，以二油酰磷脂酰丝氨酸（DOPS）作为佐剂，制备了一种寨卡病毒疫苗。该疫苗单次注射后能诱导产生高水平的特异性IgG。这些抗体在体外能够中和寨卡病毒，而不会增强登革病毒的感染。因此，这里描述的基于展示在VLP上的EDIII的疫苗能够刺激产生特异性中和寨卡病毒的抗体，而不会潜在地增强由登革病毒引起的疾病。
