Zika Virus-Derived E-DIII Protein Displayed on Immunologically Optimized VLPs Induces Neutralizing Antibodies without Causing Enhancement of Dengue Virus Infection.

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

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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-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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology
08 Faculty of Science > Departement of Chemistry and Biochemistry

UniBE Contributor:

Cabral de Miranda, Gustavo; Mohsen, Mona Omar Mahmoud; Pobelov, Ilya; Rösti, Elisa Simona and Bachmann, Martin

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

2076-393X

Publisher:

MDPI

Language:

English

Submitter:

Lee-Anne Brand

Date Deposited:

15 Nov 2019 16:37

Last Modified:

17 Nov 2020 14:43

Publisher DOI:

10.3390/vaccines7030072

Related URLs:

PubMed ID:

31340594

Uncontrolled Keywords:

Zika virus dioleoyl phosphatidylserine (DOPS) envelop (E) protein domain III (EDIII) vaccine virus like particles (VLPs)

BORIS DOI:

10.7892/boris.135089

URI:

https://boris.unibe.ch/id/eprint/135089

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