Zika Virus-Derived E-DIII Protein Displayed on Immunologically Optimized VLPs Induces Neutralizing Antibodies without Causing Enhancement of Dengue Virus Infection
| Autor: | Mona O. Mohsen, Elisa S Roesti, Stephanie M. Lim, Byron E. E. Martina, Matthias F. Kramer, Murray A. Skinner, Gustavo Cabral-Miranda, Matthew D. Heath, Martin F. Bachmann, Ilya Pobelov |
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| Přispěvatelé: | Virology |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment viruses Immunology lcsh:Medicine 610 Medicine & health virus like particles (VLPs) Dengue virus medicine.disease_cause Article Virus Zika virus Cucumber mosaic virus 03 medical and health sciences 0302 clinical medicine SDG 3 - Good Health and Well-being vaccine parasitic diseases Drug Discovery 540 Chemistry medicine Pharmacology (medical) 030212 general & internal medicine Pharmacology biology Transmission (medicine) lcsh:R virus diseases biochemical phenomena metabolism and nutrition envelop (E) protein domain III (EDIII) biology.organism_classification Virology Flavivirus dioleoyl phosphatidylserine (DOPS) 030104 developmental biology Infectious Diseases biology.protein 570 Life sciences Antibody Adjuvant |
| Zdroj: | Vaccines, 7(3):72. Multidisciplinary Digital Publishing Institute (MDPI) Vaccines Volume 7 Issue 3 Cabral-Miranda, Gustavo; Lim, Stephanie M; Mohsen, Mona O.; Pobelov, Ilya V.; Rösti, Elisa S.; Heath, Matthew D; Skinner, Murray A; Kramer, Matthias F; Martina, Byron E E; Bachmann, Martin F. (2019). Zika Virus-Derived E-DIII Protein Displayed on Immunologically Optimized VLPs Induces Neutralizing Antibodies without Causing Enhancement of Dengue Virus Infection. Vaccines, 7(3) MDPI 10.3390/vaccines7030072 Vaccines, Vol 7, Iss 3, p 72 (2019) |
| ISSN: | 2076-393X |
| DOI: | 10.7892/boris.135089 |
| Popis: | Zika virus (ZIKV) is a flavivirus similar to Dengue virus (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&ndash 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 Cucumber mosaic virus (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. |
| Databáze: | OpenAIRE |
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