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

Rahul Shukla, Rajgokul K. Shanmugam, Viswanathan Ramasamy, Upasana Arora, Gaurav Batra, Joshua A. Acklin, Florian Krammer, Jean K. Lim, Sathyamangalam Swaminathan, Navin Khanna

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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.

Original languageEnglish
Article number102738
StatePublished - Apr 2020


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


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