Administration of a microparticulate Zika vaccine using dissolving microneedle patches

Abstract

Zika is an infectious disease transmitted to humans through mosquito bites. It can lead to Guillain-Barré Syndrome. If transferred from mother to fetus, Zika can cause microcephaly. However, there is no approved treatment or vaccine available for Zika. Hence, we aim to develop a microparticulate vaccine for Zika and to investigate transdermal route for administration using microneedle patches to provide pain-free and needle-free immunization. PLGA microparticles (MP) encapsulating antigen (Zika PRVABC59) and adjuvants were formulated using double emulsion solvent evaporation. The size and zeta potential of MP were 573.4±10.18nm and -22.6±0.503mV. The encapsulation efficiency was 55-70%. Scanning electron microscopy showed that the MP were spherical. SDS-PAGE confirmed that the process did not affect antigen integrity. In vitro release study showed sustained release of antigen. MP were immunogenic and non-cytotoxic in vitro in dendritic cells. Subsequently, the vaccine MP with or without adjuvant MP were either injected IM or using microneedle patches via transdermal route to mice. Mice immunized with particulate vaccine produced significantly higher IgG, IgG1 and IgG2a antibody titers than the control group a robust humoral response as well as a balanced Th1/Th2 response. Antibody titers after transdermal immunization were comparable with titers after intramuscular immunization. Thus, this study established the feasibility of transdermal microneedle-based vaccine for Zika.