Abstract
The Zika virus (ZIKV) outbreak in the Americas and South Pacific poses a significant burden on human health because of ZIKV’s neurotropic effects in the course of fetal development. Vaccine candidates against ZIKV are coming online, but immunological tools to study anti-ZIKV responses in preclinical models, particularly T cell responses, remain sparse. We deployed RNA nanoparticle technology to create a vaccine candidate that elicited ZIKV E protein-specific IgG responses in C57BL/6 mice as assayed by ELISA. Using this tool, we identified a unique H-2Db-restricted epitope to which there was a CD8+ T cell response in mice immunized with our modified dendrimer-based RNA nanoparticle vaccine. These results demonstrate that this approach can be used to evaluate new candidate antigens and identify immune correlates without the use of live virus.
Highlights
The ongoing outbreak of Zika virus (ZIKV), a flavivirus, in Latin America and the South Pacific is associated with an increased incidence of neurological complications, including Guillain-Barré syndrome[1, 2] and fetal abnormalities, including spontaneous abortion, microencephaly, and placental insufficiency[3, 4]
We previously developed a modified dendrimer nanoparticle (MDNP)-based RNA replicon vaccine platform that provides single-dose protection in mouse models of lethal Influenza, Ebola, and Toxoplasma gondii challenges[28], and in the current study applied it to ZIKV
RNA was transcribed from the plasmid in vitro, and expression of the correct post-translationally cleaved envelope glycoprotein was confirmed by immunoblot in transfected hamster kidney cells (BHK21) after 3 days using a polyclonal antiserum against ZIKV E protein
Summary
The ongoing outbreak of Zika virus (ZIKV), a flavivirus, in Latin America and the South Pacific is associated with an increased incidence of neurological complications, including Guillain-Barré syndrome[1, 2] and fetal abnormalities, including spontaneous abortion, microencephaly, and placental insufficiency[3, 4]. Deployment of DNA-based immunoprophylactics requires electroporation or jet-injection systems[9, 10] This makes administration of the lead vaccine candidate a challenge in most of the seriously affected regions. The frequent cross-reactivity among Flavivirus species complicates serological detection of ZIKV infection or virus-specific antibodies, making studies of ZIKV-specific humoral immunity challenging[15,16,17,18,19]. Available enzyme-linked immunosorbent assay (ELISA) kits that detect anti-flaviviral antibodies suffer from cross-reactivity to other Flavivirus strains This confounds the study of multivalent flaviviral vaccines. We previously developed a modified dendrimer nanoparticle (MDNP)-based RNA replicon vaccine platform that provides single-dose protection in mouse models of lethal Influenza, Ebola, and Toxoplasma gondii challenges[28], and in the current study applied it to ZIKV. By means of T cell stimulation assays we could unambiguously distinguish between unvaccinated and vaccinated animals
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