Zika virus like particles elicit protective antibodies in mice

Abstract

Mosquito-borne Zika virus (ZIKV) typically causes a mild and self-limiting illness known as Zika fever. Since its recent emergence in 2014 in the American continent, ZIKV infection during pregnancy has been closely associated with a wide range of congenital abnormalities. To date, no vaccines or antivirals are publicly available. We developed Zika virus-like particles (VLPs) and evaluated their immunogenicity and protective efficacy in mouse models. ZIKV VLPs (ZIKVLPs) formulated with alum were injected into 6-8-week-old interferon deficient AG129 mice as well as wild type BALB/c mice. Control mice received PBS/alum. Animals were challenged with 200 PFU (>1000 AG129 LD50s) of ZIKV strain H/PF/2013. All vaccinated mice survived with no morbidity or weight loss while control animals either died at 9 days post challenge (AG129) or had increased viremia (BALB/c). Neutralizing antibodies were observed in all ZIKVLP vaccinated mice. The role of neutralizing antibodies in protecting mice was demonstrated by passive transfer. Our findings demonstrate the protective efficacy of the ZIKVLP vaccine and highlight the important role that neutralizing antibodies play in protection against ZIKV infection.

A Vaccine Based on a Modified Vaccinia Virus Ankara Vector Expressing Zika Virus Structural Proteins Controls Zika Virus Replication in Mice

“…3c ). The results showed that MVA-ZIKV formed smooth spherical particles of similar size (around 50 nm) and morphology than ZIKV VLPs produced by other ZIKV vaccines expressing prM-E genes 13 , 15 , 18 , 23 (Fig. 3c ).…”

“…Moreover, we have detected the presence of the ZIKV E protein and the mature M protein in supernatants of cells infected with MVA-ZIKV, confirming their release to the medium. Remarkably, the analysis by immunogold electron microscopy of the purified supernatants demonstrated that MVA-ZIKV produced VLPs, similarly to other ZIKV vaccines or flavivirus expressing the prM-E genes 13 , 15 , 18 , 23 . Furthermore, an additional advantage as a vector is that MVA-ZIKV is highly stable in cell culture, maintaining the expression of ZIKV antigens at least during 9 continuous passages at low MOI, with 100% of the plaques picked at passage 9 expressing the correct size ZIKV antigens.…”

“…It has been described that coexpression of flaviviral prM and E proteins results in the production of VLPs [also termed subviral particles (SVPs)] 13 , 15 – 18 . Thus, to test whether MVA-ZIKV could form VLPs, we investigated their presence in the supernatant of infected cells.…”

Next generation agents (synthetic agents): Emerging threats and challenges in detection, protection, and decontamination

“…The 10.8 kb genome of ZIKV encodes a single polyprotein that, upon action of host and viral proteases, forms three structural proteins (C, PrM, and E) and seven nonstructural proteins (NS1-5 NS2A, NS2B, NS3, NS4A, NS4B, and NS5) (Ye et al, 2016). Numerous approaches are being employed to develop live attenuated virus (Shan et al, 2017), inactivated whole virus (Sumathy et al, 2017), subunit DNA/RNA vaccines (Pardi et al, 2017;To et al, 2018), virus like particles (Espinosa et al, 2018;Salvo et al, 2018), over virus vectored (Xu et al, 2018), and chimeric ZIKV (Kum et al, 2018;Li et al, 2018) vaccines pertaining to several benefits including economical and long-term immunity. But only a few of them have generated appropriate prophylactic responses in tested in vivo models.…”

Polymeric Nanoparticles Engineered as a Vaccine Adjuvant-Delivery System

“…Unfortunately, up to now, still there are no licensed vaccines for prophylaxis of Zika, though several conventional approaches have been tried on developing such as an urgently needed products, including inactivated, recombinant live-attenuated viruses, protein subunit vaccines, RNA and DNA vaccines, as well as the VLP-based VADS [30]. Recently, using for making vaccines to defend against Zika and demonstrated that mice injected with Zika VLP combined with adjuvant alum secreted high levels of the Ag-neutralizing Abs [31]. In particular, the vaccinated mice all survived without morbidity or weight loss after receiving the lethal challenge with the dose of 200 PFU of Zika strain H/PF/2013, proving the protective efficacy of the VLP-based Zika vaccine which may be tested in humans as a prophylactic candidate with minimal safety concerns to protect unborn babies whose mothers become infected with Zika during pregnancy.…”