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Jacob Beaver, Ioanna Skountzou; Zika virus microneedle vaccination confers long-term protection to immune-privileged compartments. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6415.
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© ARVO (1962-2015); The Authors (2016-present)
Zika virus (ZIKV) has garnered global attention since outbreaks were correlated with Guillain-Barré syndrome (GBS) and congenital Zika syndrome (CZS) in newborns from infected pregnant women. Conjuctivitis/uveitis and GBS are prominent concerns during ZIKV infection, and emerging data suggests infants with CZS retain permanent ocular malformations. There is no commercial vaccine available for ZIKV and few studies characterize candidate vaccine protection of ocular and brain tissues. ZIKV is transmitted by mosquito bites, making vaccination via skin particularly advantageous, as the skin serves as the first barrier in a human host. We hypothesize that dermal vaccination using microneedle patches (MNP) will provide superior vaccine efficacy which will protect ocular and brain immune-privileged compartments from infection-induced damage.
Mice were vaccinated either intramuscular (IM) or by MNP, in a prime or prime/boost model. Vaccine-specific antibody kinetics were evaluated via ELISA before and after infectious challenge. Additionally, as the autoreactive antibodies associated with GBS can impact viral infectivity into brain and ocular tissues, we performed ELISAs to characterize antibody cross-reactivity to GD1b and GT1a, which are gangliosides implicated in GBS. We next determined the physiological impact of challenge to eyes and brain tissues through microscopy techniques in MNP and IM groups.
MNP groups demonstrate a greater induction of vaccine-specific antibodies than IM at all challenge timepoints (all p<0.0001). These same antibodies exhibit greater neutralization capacity compared to IM or unvaccinated groups (p= 0.004 to <0.0001). Despite vaccine-specific IgG concentration differences, ganglioside cross-reactivity ELISAs reveal that MNP vaccinations consistently result in lower autoantibodies than IM groups, while IM antibodies are reactive to GT1a until 80 days post vaccination. MNP vaccination results in less viral infectivity of ocular and brain tissues, and protection against leukocyte invasion into cornea and retina.
Consistent with previous MNP vaccination studies, our results demonstrate that MNP delivery of ZIKV vaccine offers an expedited antibody response, superior antibody titers, and ultimately confers protection to ocular and brain tissues, which are of paramount importance when evaluating vaccine candidates against ZIKV.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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