Elsevier

EBioMedicine

Volume 54, April 2020, 102738
EBioMedicine

Research paper
Zika virus envelope nanoparticle antibodies protect mice without risk of disease enhancement

https://doi.org/10.1016/j.ebiom.2020.102738Get rights and content
Under a Creative Commons license
open access

Abstract

Background

Zika virus (ZIKV), an arbovirus capable of causing neurological abnormalities, is a recognised human pathogen, for which a vaccine is required. As ZIKV antibodies can mediate antibody-dependent enhancement (ADE) of dengue virus (DENV) infection, a ZIKV vaccine must not only protect against ZIKV but must also not sensitise vaccinees to severe dengue.

Methods

The N-terminal 80% of ZIKV envelope protein (80E) was expressed in Pichia pastoris and its capacity to self-assemble into particulate structures evaluated using dynamic light scattering and electron microscopy. Antigenic integrity of the 80E protein was evaluated using ZIKV-specific monoclonal antibodies. Its immunogenicity and protective efficacy were assessed in BALB/c and C57BL/6 Stat2−/− mice, respectively. Its capacity to enhance DENV and ZIKV infection was assessed in AG129 and C57BL/6 Stat2−/− mice, respectively.

Findings

ZIKV-80E protein self-assembled into discrete nanoparticles (NPs), which preserved the antigenic integrity of neutralising epitopes on E domain III (EDIII) and elicited potent ZIKV-neutralising antibodies predominantly against this domain in BALB/c mice. These antibodies conferred statistically significant protection in vivo (p = 0.01, Mantel–Cox test), and did not exacerbate sub-lethal DENV-2 or ZIKV challenges in vivo.

Interpretation

Yeast-expressed ZIKV-80E, which forms highly immunogenic EDIII-displaying NPs, elicits ZIKV EDIII-specific antibodies capable of offering significant protection in vivo, without the potential risk of ADE upon subsequent DENV-2 or ZIKV infection. This offers a promising vaccine candidate for further development.

Funding

This study was supported partly by ICGEB, India, and by NIAID, USA.

Keywords

Zika virus vaccine
VLPs
Nanoparticles
Pichia pastoris;Dengue virus
Antibody-dependent enhancement
AG129
C57BL/6 Stat2−/−

Cited by (0)

1

These authors contributed equally.

2

Current address: Vaccine R & D, R & D-III, Sun Pharmaceutical Industries Ltd., Gurugram, India.